Use of melanocortins to treat insulin sensitivity

ABSTRACT

The present invention relates to peptide ligands of the melanocortin receptors, in particular the melanocortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as insulin resistance.

BACKGROUND OF THE INVENTION

Melanocortins are a family of regulatory peptides which are formed bypost-translational processing of pro-hormone pro-opiomelanocortin (POMC;131 amino acids in length). POMC is processed into three classes ofhormones; the melanocortins, adrenocorticotropin hormone, and variousendorphins (e.g. lipotropin) (Cone et al., Recent Prog. Horm. Res.,51:287-317, (1996); Cone et al., Ann. N.Y. Acad. Sci., 31:342-363,(1993)).

Five melanocortin receptors (MC-R) have been characterized to date.These include melanocyte-specific receptor (MC1-R),corticoadrenal-specific ACTH receptor (MC2-R), melanocortin-3 (MC3-R),melanocortin-4 (MC4-R) and melanocortin-5 receptor (MC5-R). All of themelanocortin receptors respond to the peptide hormone class ofmelanocyte stimulating hormones (MSH) (Cone et al., Ann. N.Y. Acad.Sci., 680:342-363 (1993); Cone et al., Recent Prog. Horm. Res.,51:287-318 (1996)).

There has been great interest in melanocortin (MC-R) receptors astargets for the design of novel therapeutics to treat disorders of bodyweight such as obesity and cachexia. One of the receptors, MC4-R, is a332 amino acid transmembrane protein expressed in brain as well asplacental and gut tissues (Cone et al., Ann. N.Y. Acad. Sci.,680:342-363 (1993); Cone et al., Recent Prog. Horm. Res., 51:287-318(1996)). Recent pharmacological confirmation has established thatcentral MC4-R receptors are the prime mediators of the anorexic andorexigenic effects reported for melanocortin agonists and antagonists,respectively (Giraudo et al., Brain Res., 809:302-306 (1998); Farooqi etal., NE J. Med., 348:1085-1095 (2003); MacNeil et al., Eu. J. Pharm.,44:141-157 (2002); MacNeil et al., Eu. J. Pharm., 450:93-109 (2002);Kask et al., NeuroReport, 10:707-711 (1999); Chen et al.,. TransgenicRes., 9:145-54, (2000); Marsh et al., Nat Genet., 21:119-22, (1999);Balthasar et al., Cell, 123:493-505 (2005)).

Complications of body weight disorders commonly include an inability toproduce and utilize insulin, often resulting in faulty glucoseregulation. The consequence of failure to properly control glucosemetabolism affects many aspects of overall health including energymetabolism, neuropathy and heart disease. Current progress withreceptor-selective melanocortin receptor ligands evidences thetherapeutic potential of melanocortin receptor activation, particularlyMC4-R, in the treatment of glucose regulation, including insulinmetabolism.

SUMMARY OF THE INVENTION

The present invention is directed to the use of peptides which areligands of one or more of the melanocortin receptors (MC-R), or thepharmaceutically-acceptable salts thereof, to treat mammals sufferingfrom insulin resistance. In one embodiment, the ligands are agonists tothe melanocortin 4 receptor. In a preferred embodiment, the melanocortinreceptor ligands are according to the formulae described herein or areselected from particular peptides described herein.

The insulin resistant subject mammals may be obese or overweight and maylose weight as a result of the administration of the peptides of theinvention. The insulin resistant subject mammals may also be normalweight or lean. The insulin resistant condition of the subject mammalsmay be treated independent of weight loss. In addition, the subjectmammals may be human subjects of any age, such as an infant, a child, anadult or an elderly adult.

In the first embodiment, the invention provides a method to treatinsulin resistance in a mammalian subject, with or without weight loss,by the administration of a therapeutically effective amount of amelanocortin receptor 4 ligand according to Formula (I) andpharmaceutically acceptable salts, hydrates, solvates or prodrugsthereof (see International Patent Application Publication Number WO2007/008704, incorporated herein by reference in its entirety):

(R²R³)-A′-c(A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹)-A¹⁰-R¹  (I)

wherein:

A′ is Acc, HN—(CH₂)_(m)—C(O), L- or D-amino acid, or deleted;

A² is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Asp, or Glu;

A³ is Gly, Ala, β-Ala, Gaba, Aib, D-amino acid, or deleted;

A⁴ is H is, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, or (X¹, X², X³, X⁴,X⁵)Phe;

A⁵ is D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X¹, X², X³, X⁴, X⁵)Phe,L-Phe or D-(Et)Tyr;

A⁶ is Arg, hArg, Dab, Dap, Lys, Orn, or HN—CH((CH₂)_(n)—N(R⁴R⁵))—C(O);

A⁷ is Trp, 1-Nal, 2-Nal, Bal, Bip, D-Trp, D-2-Nal, D-Bal or D-Bip;

A⁸ is Gly, D-Ala, Acc, Ala, 13-Ala, Gaba, Apn, Ahx, Aha,HN—(CH₂)_(s)—C(O), or deleted;

A⁹ is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Orn, or Lys;

A¹⁰ is Acc, HN—(CH₂)_(t)—C(O), L- or D-amino acid, or deleted;

R¹ is OH or NH₂;

each of R² and R³ is, independently for each occurrence, selected fromthe group consisting of H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl,(C₁-C₃₀)acyl, (C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl, aryl(C₁-C₃₀)alkyl,aryl(C₁-C₃₀)acyl, substituted (C₁-C₃₀)alkyl, substituted(C₁-C₃₀)heteroalkyl, substituted (C₁-C₃₀)acyl, substituted(C₂-C₃₀)alkenyl, substituted (C₂-C₃₀)alkynyl, substitutedaryl(C₁-C₃₀)alkyl, and substituted aryl(C₁-C₃₀)acyl;

each of R⁴ and R⁵ is, independently for each occurrence, H,(C₁-C₄₀)alkyl, (C₁-C₄₀)heteroalkyl, (C₁-C₄₀)acyl, (C₂-C₄₀)alkenyl,(C₂-C₄₀)alkynyl, aryl(C₁-C₄₀)alkyl, aryl(C₁-C₄₀)acyl, substituted(C₁-C₄₀)alkyl, substituted (C₁-C₄₀)heteroalkyl, substituted(C₁-C₄₀)acyl, substituted (C₂-C₄₀)alkenyl, substituted (C₂-C₄₀)alkynyl,substituted aryl(C₁-C₄₀)alkyl, substituted aryl(C₁-C₄₀)acyl,(C₁-C₄₀)alkylsulfonyl, or —C(NH)—NH₂;

m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;

n is, independently for each occurrence, 1, 2, 3, 4 or 5;

s is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7;

t is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7;

X′, X², X³, X⁴, and X⁸ each is, independently for each occurrence, H, F,Cl, Br, I, (C₁₋₁₀)alkyl, substituted (C₁₋₁₀)alkyl, (C₂₋₁₀)alkenyl,substituted (C₂₋₁₀)alkenyl, (C₂₋₁₀)alkynyl, substituted (C₂₋₁₀)alkynyl,aryl, substituted aryl, OH, NH₂, NO₂, or CN; provided that

-   -   (I). when R⁴ is (C₁-C₄₀)acyl, aryl(C₁-C₄₀)acyl, substituted        (C₁-C₄₀)acyl, substituted aryl(C₁-C₄₀)acyl,        (C₁-C₄₀)alkylsulfonyl, or —C(NH)—NH₂, then R⁵ is H or        (C₁-C₄₀)alkyl, (C₁-C₄₀)heteroalkyl, (C₂-C₄₀)alkenyl,        (C₂-C₄₀)alkynyl, aryl(C₁-C₄₀)alkyl, substituted (C₁-C₄₀)alkyl,        substituted (C₁-C₄₀)heteroalkyl, substituted (C₂-C₄₀)alkenyl,        substituted (C₂-C₄₀)alkynyl, or substituted aryl(C₁-C₄₀)alkyl;    -   (II). when R² is (C₁-C₃₀)acyl, aryl(C₁-C₃₀)acyl, substituted        (C₁-C₃₀)acyl, or substituted aryl(C₁-C₃₀)acyl, then R³ is H,        (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl, (C₂-C₃₀)alkenyl,        (C₂-C₃₀)alkynyl, aryl(C₁-C₃₀)alkyl, substituted (C₁-C₃₀)alkyl,        substituted (C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)alkenyl,        substituted (C₂-C₃₀)alkynyl, or substituted aryl(C₁-C₃₀)alkyl;    -   (III). either A³ or A⁸ or both must be present in said compound;    -   (IV). when A² is Cys, D-Cys, hCys, D-hCys, Pen, or D-Pen, then        A⁹ is Cys, D-Cys, hCys, D-hCys, Pen, or D-Pen;    -   (V). when A² is Asp or Glu, then A⁹ is Dab, Dap, Orn, or Lys;

(VI). when A⁸ is Ala or Gly, then A¹ is not NIe; and

(VII). when A′ is deleted, then R² and R³ cannot both be H;

or pharmaceutically acceptable salts thereof.

In one aspect of the first embodiment, the invention provides a methodto treat insulin resistance in a mammalian subject, with or withoutweight loss, by the administration of a therapeutically effective amountof a subgroup of melanocortin receptor ligands of the immediateforegoing Formula I, wherein':

-   -   A¹ is A6c, Arg, D-Arg, Cha, D-Cha, hCha, Chg, D-Chg, Gaba, Ile,        Leu, hLeu, Met, β-hMet, 2-Nal, D-2-Nal, Nip, Nle, Oic, Phe,        D-Phe, hPhe, hPro, Val, or deleted;    -   A² is Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen, or D-Pen;    -   A³ is D-Abu, Aib, Ala, β-Ala, D-Ala, D-Cha, Gaba, D-Glu, Gly,        D-Ile, D-Leu, D-Tle, D-Val, or deleted;

A⁴ is H is or 3-Pal;

A⁵ is D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-Trp, or D-(Et)Tyr;

A⁶ is Arg, or hArg;

A⁷ is Bal, Bip, 1-Nal, 2-Nal, Trp, D-Trp;

A⁸ is A6c, D-Ala, Aha, Ahx, Ala, β-Ala, Apn, Gaba, Gly or deleted;

A⁹ is Cys, D-Cys, hCys, D-hCys, Lys, Pen, or D-Pen;

A¹⁰ is Thr, or deleted;

wherein at least one of A³ or A⁸ is deleted, but not both,

or pharmaceutically acceptable salts thereof.

More preferred compounds of the immediately foregoing group of ligandsaccording to Formula (I) useful to treat insulin resistance in amammalian subject, with or without weight loss, are compounds of theformula:

SEQ ID NO: 1 Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 1Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 4Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH₂; SEQ ID NO: 5Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 11Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 12n-butanoyl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)- NH₂; SEQ ID NO: 11Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 13Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH₂; SEQ ID NO: 17n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal- Cys)-NH₂; SEQ ID NO: 17n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)- NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH₂; SEQ ID NO: 61Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 19Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH₂; SEQ ID NO: 20Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH₂; SEQ ID NO: 21Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 22Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 22Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 23D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)- Thr-NH₂; SEQ ID NO: 25D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)- Thr-NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)- Thr-NH₂; SEQ ID NO: 27Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH₂; SEQ ID NO: 29Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEQ ID NO: 30Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 31Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 32Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 32Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 33Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 34Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 34Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 35Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 36Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 37Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 40Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 40Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 41Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; SEQ ID NO: 42Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; SEQ ID NO: 42Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; SEQ ID NO: 41Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; SEQ ID NO: 44Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 29Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 44Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; SEQ ID NO: 47Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 29Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEQ ID NO: 48Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; SEQ ID NO: 49Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; SEQ ID NO: 50Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 50Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 51Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 52Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 52Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 51Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 53Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 53Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)- Thr-NH₂; SEQ ID NO: 27Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 32Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 34Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 1Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 4Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH₂; SEQ ID NO: 6Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 21Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 22Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 23D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 25D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)- Thr-NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr- NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)- Thr-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH₂; SEQ ID NO: 29Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEQ ID NO: 30Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 31Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 32Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 33Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 34Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 35Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 36Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 37Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 20Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 40Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 40Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; or SEQ ID NO: 49Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂;or pharmaceutically acceptable salts thereof.

In the second embodiment, the invention provides a method to treatinsulin resistance in a mammalian subject, with or without weight loss,by the administration of a therapeutically effective amount of amelanocortin receptor ligand according to Formula (II) andpharmaceutically acceptable salts, hydrates, solvates or prodrugsthereof (see International Patent Application Publication Number WO2007/008704 incorporated herein by reference in its entirety):

(R²R³)-A¹-c(A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹)-NH₂  (II)

wherein:

A′ is Nle or deleted;

A² is Cys or Asp;

A³ is Glu or D-Ala;

A⁴ is H is;

A⁵ is D-Phe;

A⁶ is Arg;

A⁷ is Trp, 2-Nal or Bal;

A⁸ is Gly, Ala, D-Ala, (3-Ala, Gaba or Apn;

A⁹ is Cys or Lys;

each of R² and R³ is independently selected from the group consisting ofH or (C₁-C₆)acyl;

provided that

(I). when R² is (C₁-C₆)acyl, then R³ is H; and

(II). when A² is Cys, then A⁹ is Cys,

or a pharmaceutically acceptable salt thereof.

More preferred of the immediately foregoing group of compounds which areuseful to treat insulin resistance in a mammalian subject, with orwithout weight loss, are compounds of the formula:

SEQ ID NO: 54 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH₂; SEQ IDNO: 54 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)- NH₂; SEQ ID NO:54 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)- NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)- NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 55Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 55Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH₂; SEQ ID NO: 56Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 56Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH₂; SEQ ID NO: 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)- NH₂; SEQ ID NO: 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)- NH₂; SEQ ID NO: 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)- NH₂; or SEQ ID NO: 58Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH₂;or a pharmaceutically acceptable salt thereof.

In the third embodiment, the invention provides a method to treatinsulin resistance in a mammalian subject, with or without weight loss,by the administration of a therapeutically effective amount of amelanocortin receptor compound according to Formula (III), andpharmaceutically acceptable salts, hydrates, solvates or prodrugsthereof (see International Application Publication Number WO2007/008684, incorporated herein by reference in its entirety):

(R²R³)—B¹-A¹-c(A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹)-A¹⁰-A¹¹-A¹²-A¹³-B²—B³—R¹  (III)

wherein:

B¹ is a peptide moiety which contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,or 15 amino acids, wherein at least 5 amino acids are independentlyselected from the group consisting of L-Arg, D-Arg, L-hArg and D-hArg,or B¹ is optionally deleted;

A¹ is Acc, HN—(CH₂)_(m)—C(O), L- or D-amino acid or deleted;

A² is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Asp or Glu;

A³ is Gly, Glu, Ala, β-Ala, Gaba, Aib, D-amino acid or deleted;

A⁴ is H is, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi or (X′, X², X³, X⁴,X⁵)Phe;

A⁵ is D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X¹, X², X³, X⁴, X⁵)Phe,D-(Et)Tyr, D-Dip, D-Bip or D-Bpa;

A⁶ is Arg, hArg, Dab, Dap, Lys, Orn or HN—CH((CH₂)_(n)—N(R⁴R⁵))—C(O);

A⁷ is Trp, 1-Nal, 2-Nal, Bal, Bip, Dip, Bpa, D-Trp, D-1-Nal, D-2-Nal,D-Bal, D-Bip, D-Dip or D-Bpa;

A⁸ is Gly, D-Ala, Acc, Ala, β-Ala, Gaba, Apn, Ahx, Aha,HN—(CH₂)_(s)—C(O) or deleted;

A⁹ is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Orn or Lys;

A¹⁰ is Acc, HN—(CH₂)_(t)—C(O), Pro, hPro, 3-Hyp, 4-Hyp, Thr, an L- orD-amino acid or deleted;

A¹¹ is Pro, hPro, 3-Hyp, 4-Hyp or deleted;

A¹² is Lys, Dab, Dap, Arg, hArg or deleted;

A¹³ is Asp, Glu or deleted;

B² is a peptide moiety containing 1, 2, 3, 4, or 5 amino acids ordeleted,

B³ is a peptide moiety which contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14or 15 amino acids wherein at least 5 amino acids are independentlyselected from the group consisting of L-Arg, D-Arg, L-hArg and D-hArg,or is deleted;

R¹ is OH or NH₂;

R² and R³ each is, independently for each occurrence, selected from thegroup consisting of H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl, (C₁-C₃₀)acyl,(C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl, aryl(C₁-C₃₀)alkyl, aryl(C₁-C₃₀)acyl,substituted (C₁-C₃₀)alkyl, substituted (C₁-C₃₀)heteroalkyl, substituted(C₁-C₃₀)acyl, substituted (C₂-C₃₀)alkenyl, substituted (C₂-C₃₀)alkynyl,substituted aryl(C₁-C₃₀)alkyl and substituted aryl(C₁-C₃₀)acyl;

R⁴ and R⁵ each is, independently for each occurrence, H, (C₁-C₄₀)alkyl,(C₁-C₄₀)heteroalkyl, (C₁-C₄₀)acyl, (C₂-C₄₀)alkenyl, (C₂-C₄₀)alkynyl,aryl(C₁-C₄₀)alkyl, aryl(C₁-C₄₀)acyl, substituted (C₁-C₄₀)alkyl,substituted (C₁-C₄₀)heteroalkyl, substituted (C₁-C₄₀)acyl, substituted(C₂-C₄₀)alkenyl, substituted (C₂-C₄₀)alkynyl, substitutedaryl(C₁-C₄₀)alkyl, substituted aryl(C₁-C₄₀)acyl, (C₁-C₄₀)alkylsulfonylor C(NH)—NH₂;

n is, independently for each occurrence, 1, 2, 3, 4 or 5;

m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;

s is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;

t is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;

X¹, X², X³, X⁴ and X⁵ each is, independently for each occurrence, H, F,Cl, Br, I, (C₁₋₁₀)alkyl, substituted (C₁₋₁₀)alkyl, (C₂₋₁₀)alkenyl,substituted (C₂₋₁₀)alkenyl, (C₂-10)alkynyl, substituted (C₂₋₁₀)alkynyl,aryl, substituted aryl, OH, NH₂, NO₂ or CN; provided that:

(I) when R⁴ is (C₁-C₄₀)acyl, aryl(C₁-C₄₀)acyl, substituted (C₁-C₄₀)acyl,substituted aryl(C₁-C₄₀)acyl, (C₁-C₄₀)alkylsulfonyl or C(NH)—NH₂, thenR⁵ is H, (C₁-C₄₀)alkyl, (C₁-C₄₀)heteroalkyl, (C₂-C₄₀)alkenyl,(C₂-C₄₀)alkynyl, aryl(C₁-C₄₀)alkyl, substituted (C₁-C₄₀)alkyl,substituted (C₁-C₄₀)heteroalkyl, substituted (C₂-C₄₀)alkenyl,substituted (C₂-C₄₀)alkynyl or substituted aryl(C₁-C₄₀)alkyl;

(II) when R² is (C₁-C₃₀)acyl, aryl(C₁-C₃₀)acyl, substituted (C₁-C₃₀)acylor substituted aryl(C₁-C₃₀)acyl, then R³ is H, (C₁-C₃₀)alkyl,(C₁-C₃₀)heteroalkyl, (C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl,aryl(C₁-C₃₀)alkyl, substituted (C₁-C₃₀)alkyl, substituted(C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)alkenyl, substituted(C₂-C₃₀)alkynyl or substituted aryl(C₁-C₃₀)alkyl;

(III) neither B¹ nor B² contains one or more of the following amino acidsequences: Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃,Tyr-Ala-Arg-Lys-Ala-(Arg)₂-Gln-Ala-(Arg)₂,Tyr-Ala-Arg-(Ala)₂-(Arg)₂-(Ala)₂-(Arg)₂, Tyr-Ala-(Arg)₉,Tyr-(Ala)₃-(Arg)₇, Tyr-Ala-Arg-Ala-Pro-(Arg)₂-Ala-(Arg)₃ orTyr-Ala-Arg-Ala-Pro-(Arg)₂-Pro-(Arg)₂;

(IV) either B¹ or B² or both must be present in said compound;

(V) when A² is Cys, D-Cys, hCys, D-hCys, Pen or D-Pen, then A⁹ is Cys,D-Cys, hCys, D-hCys, Pen or D-Pen; and

(VI) when A² is Asp or Glu, then A⁹ is Dab, Dap, Orn or Lys;

or pharmaceutically acceptable salts thereof.

In one aspect of the third embodiment, the invention is directed to theuse of compounds of Formula (III) to treat insulin resistance in amammalian subject, with or without weight loss, wherein

B¹ is Arg-Lys-Gln-Lys-(Arg)₅, Arg-(Lys)₂-Arg-Gln-(Arg)₄,Arg-(Lys)₂-(Arg)₃-Gln-(Arg)₂, Arg-(Lys)₂-(Arg)₄-Gln-Arg,Arg-(Lys)₂-(Arg)₅-Gln, Arg-(Lys)₂-Gln-(Arg)₅, Arg-Gln-(Lys)₂-(Arg)₅,Arg-Gln-(Arg)₇, Arg-Gln-(Arg)₈, (Arg)₂-Gln-(Arg)₆, (Arg)₂-Gln-(Arg)₇,(Arg)₃-Gln-(Arg)₅, (Arg)₃-Gln-(Arg)₆, (Arg)₄-Gln-(Arg)₄,(Arg)₄-Gln-(Arg)₅, (Arg)₅, (Arg)₅-Gln-(Arg)₃, (Arg)₅-Gln-(Arg)₄, (Arg)₆,(Arg)₆-Gln-(Arg)₃, (Arg)₇, (Arg)₇-Gln-(Arg)₂, (Arg)₈, (Arg)s-Gln-Arg,(Arg)₉, (Arg)₉-Gln, (D-Arg)₅, (D-Arg)₆, (D-Arg)₇, (D-Arg)₈, (D-Arg)₉,Gln-Arg-(Lys)₂-(Arg)₅, Gln-(Arg)₈, Gln-(Arg)₉,Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃,Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-Doc; or deleted;

B² is β-Ala, β-Ala-Gly, β-Ala-Tyr, β-Ala-Tyr-Gly, (β-Ala)₂,(β-Ala)₂-Gly, (β-Ala)₂-Tyr, (β-Ala)₂-Tyr-Gly, Doc, Doc-Gly, Doc-Tyr,Doc-Tyr-Gly, (Doc)₂, (Doc)₂-Gly, (Doc)₂-Tyr, Doc)₂-Tyr-Gly, or deleted;

B³ is Arg-Lys-Gln-Lys-(Arg)₅, Arg-Lys-(Arg)₃-Gln-(Arg)₃,Arg-(Lys)₂-Arg-Gln-(Arg)₄, Arg-(Lys)₂-Gln-(Arg)₅,Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃, Arg-(Lys)₂-(Arg)₃-Gln-(Arg)₂,Arg-(Lys)₂-(Arg)₄-Gln-Arg, Arg-(Lys)₂-(Arg)₅-Gln, Arg-Gln-(Lys)₂-(Arg)₅,Arg-Gln-(Arg)₇, Arg-Gln-(Arg)_(s), (Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃,(Arg)₂-Gln-(Arg)₆, (Arg)₂-Gln-(Arg)₇, (Arg)₃-Gln-(Arg)₅,(Arg)₃-Gln-(Arg)₆, (Arg)₄-Gln-(Arg)₄, (Arg)₄-Gln-(Arg)₅, (Arg)₅,(Arg)_(s)-Gln-(Arg)₃, (Arg)₅-Gln-(Arg)₄, (Arg)₆, (Arg)₆-Gln-(Arg)₃,(Arg)₇, (Arg)₇-Gln-(Arg)₂, (Arg)₈, (Arg)s-Gln-Arg, (Arg)₉, (Arg)₉-Gln,(D-Arg)₅, (D-Arg)₆, (D-Arg)₇, (D-Arg)₈, (D-Arg)₉, Gln-Arg-(Lys)₂-(Arg)₅,Gln-(Arg)₈, Gln-(Arg)₉, or deleted;

A¹ is A6c, Cha, hCha, Chg, D-Chg, hChg, Gaba, hLeu, Met, β-hMet,D-2-Nal, Nip, Nle, Oic, Phe, D-Phe, hPhe, hPro, or deleted;

A² is Cys

A³ is D-Abu, Aib, Ala, β-Ala, D-Ala, D-Cha, Gaba, Glu, Gly, D-Ile,D-Leu, D-Met, D-Nle, D-Phe, D-Tle, D-Trp, D-Tyr, D-Val, or deleted;

A⁴ is H is;

A⁵ is D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-(X¹, X², X³, X⁴, X⁵)Phe, D-Trp,or D-(Et)Tyr;

A⁶ is Arg or hArg;

A⁷ is Bal, Bip, 1-Nal, 2-Nal, Trp, or D-Trp;

A⁸ is A5c, A6c, Aha, Ahx, Ala, β-Ala, Apn, Gaba, Gly, or deleted;

A⁹ is Cys, D-Cys, hCys, D-hCys, Lys, Pen, or D-Pen;

A¹⁰ is Pro, Thr or deleted;

A¹¹ is Pro or deleted;

A¹² is arg, Lys, or deleted;

A¹³ is Asp or deleted;

each of R² and R³ is, independently, H or acyl;

or pharmaceutically acceptable salts thereof.

Preferred ligands of the immeduiately foregoing group of compoundsaccording to Formula (III), useful to treat insulin resistance in amammalian subject, with or without weight loss, are compounds of theformula:

(SEQ ID NO: 60)Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH₂;(SEQ ID NO: 61)Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH₂; (SEQ ID NO: 62)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 62)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 63)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 64)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)₂-Lys-Asp-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 65)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 66)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 67)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 68)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 69)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 69)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 70)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 72)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 73)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 74)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 75)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂; (SEQ ID NO: 76)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Gln-(Arg)₅-NH₂; (SEQ ID NO: 77)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)₅-NH₂; (SEQ ID NO: 78)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₄-Gln-Arg-NH₂; (SEQ ID NO: 79)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 80)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 80)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 84)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 85)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₃-Gln-(Arg)₂-NH₂; (SEQ ID NO: 86)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)₂-(Arg)₅-NH₂; (SEQ ID NO: 87)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₅-Gln-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 89)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 90)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 91)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 93)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 94)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 95)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 96)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 97)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 98)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 99)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 100)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 102)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 103)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 104)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 105)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 100)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 102)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 103)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 106)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂; (SEQ ID NO: 107)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Gln-(Arg)₅-NH₂; (SEQ ID NO: 108)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)₅-NH₂; (SEQ ID NO: 109)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)₂-(Arg)₅-NH₂; (SEQ ID NO: 110)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₃-Gln-(Arg)₂-NH₂; (SEQ ID NO: 111)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₄-Gln-Arg-NH₂; (SEQ ID NO: 112)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₅-Gln-NH₂; (SEQ ID NO: 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 117)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 117)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 118)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 118)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 119)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 119)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 123)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 123)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 124)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 124)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 126)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 126)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 128)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 128)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 129)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 129)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 130)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 130)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 131)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 131)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 132)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 133)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 133)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 134)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 134)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 135)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 135)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 137)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂; (SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 139)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 140)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 143)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 144)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂;(SEQ ID NO: 145)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂; (SEQ ID NO: 146)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 148)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 147)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 147)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 148)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 149)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 149)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 151)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 151)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 152)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 152)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 154)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 153)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 153)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 154)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 155)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 155)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 157)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 156)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 156)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 157)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 158)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 158)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 159)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 160)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 161)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 162)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 164)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 163)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 163)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 164)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 165)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 165)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 166)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 166)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 168)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 167)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 167)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 168)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 170)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 169)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 169)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 170)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 171)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 171)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 173)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 172)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 172)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 173)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 175)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 176)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 177)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 178)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 179)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 180)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 181)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 182)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 183)Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 184)Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 183)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 185)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 186)Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 185)Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 186)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 187)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 189)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 190)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 189)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 190)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 191)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 191)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 193)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 194)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 193)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 194)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 195)Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 196)Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 197)Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 198)Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 199)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 199)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 201)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 202)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 203)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 203)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 204)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 204)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 207)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 206)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 206)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 207)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 208)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 208)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 209)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 210)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 209)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 211)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 212)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 213)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 213)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 267)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 214)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 216)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 214)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 217)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 215)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 216)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 215)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 217)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 220)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 224)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 225)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 224)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 225)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 226)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 229)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 230)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 232)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 231)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 232)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 233)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 234)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 235)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 236)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 235)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 236)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 237)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 238)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 237)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 238)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 239)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 240)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 239)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 240)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 241)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 242)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 241)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 242)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 243)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 243)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 245)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 246)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 245)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 246)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 247)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 247)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 249)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 250)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 249)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 250)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 251)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 251)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 253)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 254)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 253)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 254)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 255)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 255)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 257)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 258)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 257)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 258)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 259)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 260)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 259)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 260)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 261)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 262)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 261)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 262)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 263)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 264)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 263)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 264)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 265)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 266)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 265)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;or (SEQ ID NO: 266)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;;or pharmaceutically acceptable salts thereof.

In a fourth embodiment, the invention provides a method to treat insulinresistance in a mammalian subject, with or without weight loss, by theadministration of a therapeutically effective amount of a melanocortinreceptor compound according to Formula (IV), and pharmaceuticallyacceptable salts, hydrates, solvates and prodrugs thereof, with acompound having the following formula (formula (IV)):

Ac-c(Cys-Glu-His-A¹-Arg-A²-A³-Cys)-(Pro)₂-Lys-Asp-NH₂  (IV)

wherein:A¹ is the D-isomer of X-Phe or 2-Nal where X is halogen;

A² is Bal, 1-Nal, 2-Nal, or Trp; and A³ is Aib, Ala, β-Ala or Gly,

or pharmaceutically acceptable salts thereof.

Preferred compounds of the immediately foregoing formula discovered totreat insulin resistance in a mammalian subject, with or without weightloss, include the following:

(SEQ ID NO: 268)Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-NH_(2;) (SEQID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 269) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂;(SEQ ID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 2690) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂;(SEQ ID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; or(SEQ ID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)₂-Lys-Asp-NH₂;or pharmaceutically acceptable salts thereof.

The invention additionally provides a method to treat insulin resistancein a mammalian subject, with or without weight loss, by theadministration of a therapeutically effective amount of a melanocortinreceptor compound modified with a hydantoin moiety according to Formula(V), (VI) or (VII), and pharmaceutically acceptable salts, hydrates,solvates or prodrugs thereof.

According to a fifth embodiment, the invention provides a method totreat insulin resistance in a mammalian subject, with or without weightloss, by the administration of a therapeutically effective amount of amelanocortin receptor ligand according to the following formula (Formula(V)), pharmaceutically-acceptable salts, hydrates, solvates and/orprodrugs thereof (see International Patent Application NumberPCT/US08/06675 incorporated herein by reference in its entirety):

wherein

X is selected from the group consisting of —CH₂—S—S—CH₂—,—C(CH₃)₂—S—S—CH₂—, —CH₂—S—S—C(CH₃)₂—, —C(CH₃)₂—S—S—C(CH₃)₂—,—(CH₂)₂—S—S—CH₂—, —CH₂—S—S—(CH₂)₂—, —(CH₂)₂—S—S—(CH₂)₂—,—C(CH₃)₂—S—S—(CH₂)₂—, —(CH₂)₂—S—S—C(CH₃)₂—,—(CH₂)_(t)—C(O)—NR⁸—(CH₂)_(r)— and —(CH₂)_(r)—NR⁸—C(O)—(CH₂)_(t)—;

Wand R² each is, independently, H, (C₁-C₁₀)alkyl or substituted(C₁-C₁₀)alkyl;

R³ is —OH or —NH₂;

R⁴ and R⁵ each is, independently, H, (C₁-C₁₀)alkyl or substituted(C₁-C₁₀)alkyl;

X¹ is

A¹ is H is, 2-Pal, 3-Pal, 4-Pal, (X¹, X², X³, X⁴, X⁵)Phe, Taz, 2-Thi,3-Thi or is deleted;

A² is D-Bal, D-1-Nal, D-2-Nal, D-Phe or D-(X¹, X², X³, X⁴, X⁵)Phe;

A³ is Arg, hArg, Dab, Dap, Lys or Orn;

A⁴ is Bal, 1-Nal, 2-Nal, (X¹, X², X³, X⁴, X⁵)Phe or Trp;

R⁶ and R⁷ each is, independently for each occurrence thereof, H,(C₁-C₁₀)heteroalkyl, aryl(C₁-C₅)alkyl, substituted (C₁-C₁₀)alkyl,substituted (C₁-C₁₀)heteroalkyl or substituted aryl(C₁-C₅)alkyl providedthat R⁶ and R⁷ may be joined together to form a ring;

R⁸ is H, (C₁-C₁₀)alkyl or substituted (C₁-C₁₀)alkyl;

r is, independently for each occurrence thereof, 1, 2, 3, 4 or 5; and

t is, independently for each occurrence thereof, 1 or 2.

Preferrably, a compound according the foregoing formula found useful totreat insulin resistance in a mammalian subject, with or without weightloss, include compounds wherein X¹ is selected from the group consistingof:

Representative embodiments of the foregoing class of compounds useful totreat insulin resistance in a mammalian subject, with or without weightloss, are as follows:

(SEQ ID NO: 271)c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ ID NO:271) c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 272) c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH₂; or(SEQ ID NO: 272)c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH₂; (SEQ ID NO:273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ IDNO: 273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH₂; (SEQID NO: 273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH₂; or(SEQ ID NO: 273)c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH₂ (SEQ ID NO: 274)c[Hydantoin(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 274)c[Hydantoin(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 274)c[Hydantoin(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 275)c[Hydantoin(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 275)c[Hydantoin(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 275)c[Hydantoin(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 274)c[Hydantoin(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 274)c[Hydantoin(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 275)c[Hydantoin(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 275)c[Hydantoin(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO: 275)c[Hydantoin-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH₂ (SEQ ID NO: 275)c[Hydantoin-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH₂ (SEQ ID NO: 276)c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH₂; (SEQ ID NO:276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH₂; or (SEQID NO: 276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH_(2,)(SEQ ID NO: 277) c[Hydantoin(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH₂

According to a sixth embodiment, the invention provides a method totreat insulin resistance in a mammalian subject, with or without weightloss, by the administration of a therapeutically effective amount of amelanocortin receptor compound according to Formula (VI),pharmaceutically-acceptable salts, hydrates, solvates and/or prodrugsthereof (see International Patent Application Number PCT/US08/06675which is incorporated herein by reference in its entirety):

wherein

X¹ is

X² is

A¹ is Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen or D-Pen;

A² is an L- or D-amino acid;

A³ is H is, 2-Pal, 3-Pal, 4-Pal, (X¹, X², X³, X⁴, X⁵)Phe, Taz, 2-Thi or3-Thi;

A⁴ is D-Bal, D-1-Nal, D-2-Nal, D-Phe or D-(X¹, X², X³, X⁴, X⁵)Phe;

A⁵ is Arg, hArg, Dab, Dap, Lys or Orn;

A⁶ is Bal, 1-Nal, 2-Nal, (X¹, X², X³, X⁴, X⁵)Phe or Trp;

A⁷ is Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen or D-Pen;

R¹ is H, (C₁-C₁₀)alkyl or substituted (C₁-C₁₀)alkyl;

R² and R³ each is, independently, H, (C₁-C₁₀)alkyl, (C₁-C₁₀)heteroalkyl,aryl(C₁-C₅)alkyl, substituted (C₁-C₁₀)alkyl, substituted(C₁-C₁₀)heteroalkyl or substituted aryl(C₁-C₅)alkyl or R² and R³ may befused together form a cyclic moiety;

R⁴ is CO₂H or C(O)NH₂;

R⁵ and R⁶ each is, independently, H, (C₁-00)alkyl, (C₁-C₁₀)heteroalkyl,aryl(C₁-C₅)alkyl, substituted (C₁-C₁₀)alkyl, substituted(C₁-C₁₀)heteroalkyl or substituted aryl(C₁-C₅)alkyl or R⁵ and R⁶ may befused together form a cyclic moiety;

R⁷ and R⁸ each is, independently, H, (C₁-C₁₀)alkyl, (C₁-C₁₀)heteroalkyl,aryl(C₁-C₅)alkyl, substituted (C₁-C₁₀)alkyl, substituted(C₁-C₁₀)heteroalkyl or substituted aryl(C₁-C₅)alkyl; or R⁷ and R⁸ may befused together form a cyclic moiety;

R⁹ is H, (C₁-C₁₀)alkyl or substituted (C₁-C₁₀)alkyl; and

n is, independently for each occurrence thereof, 1, 2, 3, 4, 5, 6 or 7;

or a pharmaceutically acceptable salt thereof.

A preferred class of compounds according to Formula (VI) useful to treatinsulin resistance in a mammalian subject, with or without weight loss,are those compounds wherein:

A¹ is Cys;

A² is D-Ala, Asn, Asp, Gln, Glu or D-Phe;

A³ is H is;

A⁴ is D-2-Nal or D-Phe;

A⁵ is Arg;

A⁶ is Trp; and

A⁷ is Cys or Pen;

each of R′, R², R³, and R⁹ is, independently, H;

R⁴ is C(O)NH₂;

each of R⁵ and R⁶ is, independently, H, (C₁-C₁₀)heteroalkyl, substituted(C₁-C₁₀)alkyl or substituted (C₁-C₁₀)heteroalkyl or R⁵ and R⁶ may befused together form a cyclic moiety; and

-   -   each of R⁷ and R⁸ is, independently, H, (C₁-C₁₀)alkyl,        (C₁-C₁₀)heteroalkyl, substituted (C₁-C₁₀)alkyl or substituted        (C₁-C₁₀)heteroalkyl;        or pharmaceutically acceptable salts thereof.

Preferred compounds of the immediately foregoing formula (Formula (VI))useful to treat insulin resistance in a mammalian subject, with orwithout weight loss, include:

(SEQ ID NO: 278)Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 278) Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 278)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 279)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 281)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 281)Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 278)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 278)Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 282)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 282)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 278)Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 278) Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 279)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 278)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 278)Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 279)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; or(SEQ ID NO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 283)Hydantoin(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 283) Hydantoin(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 283)Hydantoin(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 284)Hydantoin(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; or(SEQ ID NO: 284)Hydantoin(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 285)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 285)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 286)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 286)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 287)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 287)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 288)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; and(SEQ ID NO: 288)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 289)Hydantoin(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;or pharmaceutically acceptable salts thereof.

In a seventh embodiment, the invention provides a method to treatinsulin resistance in a mammalian subject, with or without weight loss,by the administration of a therapeutically effective amount of amelanocortin receptor ligand belonging to a class of cyclic peptideanalogs that are ligands for the melanocortin receptors having astructure according to Formula (VII) as depicted below (seeInternational Patent Application Number PCT/US08/06675 which isincorporated herein by reference in its entirety):

wherein

X is selected from the group consisting of —CH₂—S—S—CH₂—,—C(CH₃)₂—S—S—CH₂—, —CH₂—S—S—C(CH₃)₂—, —C(CH₃)₂—S—S—C(CH₃)_(z)—,—(CH₂)₂—S—S—CH₂—, —CH₂—S—S—(CH₂)₂, (CH₂)₂—S—S—(CH₂)₂—,—C(CH₃)₂—S—S—(CH₂)₂—, —(CH₂)₂—S—S—C(CH₃)₂—,—(CH₂)_(t)—C(O)—NR⁸—(CH₂)_(r)— and —(CH₂)_(r)—NR⁸—C(O)—(CH₂)_(t)—;

each of R¹ and R⁵ is, independently, H, (C₁-C₁₀)alkyl or substituted(C₁-C₁₀)alkyl;

each of R² and R³ is, independently, H, (C₁-C₁₀)alkyl,(C₁-00)heteroalkyl, aryl(C₁-C₅)alkyl, substituted (C₁-C₁₀)alkyl,substituted (C₁-C₁₀)heteroalkyl or substituted aryl(C₁-C₅)alkyl or R²and R³ may be fused together to form a ring;

R⁴ is OH or NH₂;

each of R⁶ and R⁷ is, independently, H, (C₁-C₁₀)alkyl or substituted(C₁-C₁₀)alkyl;

A¹ is an L- or D-amino acid or deleted;

A² is H is, 2-Pal, 3-Pal, 4-Pal, (X¹, X², X³, X⁴, X⁵)Phe, Taz, 2-Thi or3-Thi;

A³ is D-Bal, D-1-Nal, D-2-Nal, D-Phe or D-(X¹, X², X³, X⁴, X⁵)Phe;

A⁴ is Arg, hArg, Dab, Dap, Lys or Orn;

A⁵ is Bal, 1-Nal, 2-Nal, (X¹, X², X³, X⁴, X⁵)Phe or Trp;

r is, independently for each occurrence thereof, 1, 2, 3, 4 or 5; and

t is, independently for each occurrence thereof, 1 or 2;

or pharmaceutically acceptable salts thereof.

In the preferred aspect of the compounds according to Formula (VII)useful to treat insulin resistance in a mammalian subject, with orwithout weight loss,

A¹ is Ala, D-Ala, Asn, Asp, Gln, Glu or Gly;

or pharmaceutically acceptable salts thereof.

Preferred compounds according to Formula (VII) useful in the treatmentof insulin resistance in a mammalian subject, include the followingcompounds:

(SEQ ID NO: 290)c[Hydantoin(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;or (SEQ ID NO: 291)c[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH₂; or (SEQ IDNO: 291) c[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH₂;or pharmaceutically acceptable salts thereof.

In an eighth embodiment, the present invention is directed to a methodto treat insulin resistance in a mammalian subject, with or withoutweight loss, by the administration of a therapeutically effective amountof a melanocortin receptor ligand according to Formula (VIII) (seeInternational Patent Application Number PCT/US08/07411, incorporatedherein by reference in its entirety):

(R²R³)-A⁰-A¹-c(A²-A³-A⁴-A⁵-A⁶-A⁷-A⁸-A⁹)-A¹⁰-R¹  (VIII)

wherein:

A⁰ is an aromatic amino acid

A¹ is Acc, HN—(CH₂)_(m)—C(O), an L- or D-amino acid;

A² is Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen, or D-Pen;

A³ is Aib, Ala, β-Ala, Gaba, Gly or a D-amino acid;

A⁴ is H is, 2-Pal, 3-Pal, 4-Pal, (X¹, X², X³, X⁴, X⁵)Phe, Taz, 2-Thi, or3-Thi;

A⁵ is D-Bal, D-1-Nal, D-2-Nal, D-Phe, L-Phe, D-(X¹, X², X³, X⁴, X⁵)Phe,L-Phe, D-Trp or D-(Et)Tyr;

A⁶ is Arg, hArg, Dab, Dap, Lys, Orn, or HN—CH((CH₂)_(n)—N(R⁴R⁵))—C(O);

A⁷ is Bal, D-Bal, Bip, D-Bip, 1-Nal, D-1-Nal, 2-Nal, D-2-Nal, or D-Trp;

A⁸ is Acc, Aha, Ahx, Ala, D-Ala, β-Ala, Apn, Gaba, Gly,HN—(CH₂)_(s)—C(O), or deleted;

A⁹ is Cys, D-Cys, hCys, D-hCys, Dab, Dap, Lys, Orn, Pen, or D-Pen;

A¹⁰ is Acc, HN—(CH₂)_(t)—C(O), L- or D-amino acid, or deleted;

R¹ is OH, or NH₂;

each of R² and R³ is, independently for each occurrence selected fromthe group consisting of H, (C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl,(C₁-C₃₀)acyl, (C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl, aryl(C₁-C₃₀)alkyl,aryl(C₁-C₃₀)acyl, substituted (C₁-C₃₀)alkyl, substituted(C₁-C₃₀)heteroalkyl, substituted (C₁-C₃₀)acyl, substituted(C₂-C₃₀)alkenyl, substituted (C₂-C₃₀)alkynyl, substitutedaryl(C₁-C₃₀)alkyl, and substituted aryl(C₁-C₃₀)acyl;

each of R⁴ and R⁵ is, independently for each occurrence, H,(C₁-C₄₀)alkyl, (C₁-C₄₀)heteroalkyl, (C₁-C₄₀)acyl, (C₂-C₄₀)alkenyl,(C₂-C₄₀)alkynyl, aryl(C₁-C₄₀)alkyl, aryl(C₁-C₄₀)acyl, substituted(C₁-C₄₀)alkyl, substituted (C₁-C₄₀)heteroalkyl, substituted(C₁-C₄₀)acyl, substituted (C₂-C₄₀)alkenyl, substituted (C₂-C₄₀)alkynyl,substituted aryl(C₁-C₄₀)allyl, substituted aryl(C₁-C₄₀)acyl,(C₁-C₄₀)alkylsulfonyl, or —C(NH)—NH₂;

m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;

n is, independently for each occurrence, 1, 2, 3, 4 or 5;

s is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7;

t is, independently for each occurrence, 1, 2, 3, 4, 5, 6, or 7;

X¹, X², X³, X⁴, and X⁵ each is, independently for each occurrence, H, F,Cl, Br, I, (C₁₋₁₀)alkyl, substituted (C₁₋₁₀)alkyl, (C₂₋₁₀)alkenyl,substituted (C₂₋₁₀)alkenyl, (C₂₋₁₀)alkynyl, substituted (C₂₋₁₀)alkynyl,aryl, substituted aryl, OH, NH₂, NO₂, or CN; provided that

(I). when R⁴ is (C₁-C₄₀)acyl, aryl(C₁-C₄₀)acyl, substituted(C₁-C₄₀)acyl,

substituted aryl(C₁-C₄₀)acyl, (C₁-C₄₀)alkylsulfonyl, or —C(NH)—NH₂, thenR⁵ is H or (C₁-C₄₀)alkyl, (C₁-C₄₀)heteroalkyl, (C₂-C₄₀)alkenyl,(C₂-C₄₀)alkynyl, aryl(C₁-C₄₀)alkyl, substituted (C₁-C₄₀)alkyl,substituted (C₁-C₄₀)heteroalkyl, substituted (C₂-C₄₀)alkenyl,substituted (C₂-C₄₀)alkynyl, or substituted aryl(C₁-C₄₀)alkyl;

(II). when R² is (C₁-C₃₀)acyl, aryl(C₁-C₃₀)acyl, substituted(C₁-C₃₀)acyl, or substituted aryl(C₁-C₃₀)acyl, then R³ is H,(C₁-C₃₀)alkyl, (C₁-C₃₀)heteroalkyl, (C₂-C₃₀)alkenyl, (C₂-C₃₀)alkynyl,aryl(C₁-C₃₀)alkyl, substituted (C₁-C₃₀)alkyl, substituted(C₁-C₃₀)heteroalkyl, substituted (C₂-C₃₀)alkenyl, substituted(C₂-C₃₀)alkynyl, or substituted aryl(C₁-C₃₀)alkyl;

(III). when A² is Cys, D-Cys, hCys, D-hCys, Pen, or D-Pen, then A⁹ isCys, D-Cys, hCys, D-hCys, Pen, or D-Pen;

(IV). when A² is Asp or Glu, then A⁹ is Dab, Dap, Orn, or Lys;

(V). when A⁸ is Ala or Gly, then A¹ is not Nle; or pharmaceuticallyacceptable salts thereof.

A preferred group of compounds of the immediate foregoing formula usefulto treat insulin resistance in a mammalian subject, with or withoutweight loss, is wherein

A⁰ is 1-Nal, 2-Nal, H is, Pff, Phe, Trp, or Tyr;

A¹ is Arg;

A² is Cys;

A³ is D-Ala;

A⁴ is H is;

A⁵ is D-Phe

A⁶ is Arg;

A⁷ is Trp

A⁸ is deleted;

A⁹ is Cys; and

A¹⁰ is deleted;

or pharmaceutically acceptable salts thereof.

Preferred compounds of the immediately foregoing group of compounds iswhich are useful to treat insulin resistance in a mammalian subject,with or without weight loss, of the formula:

(SEQ ID NO: 292) Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 292) Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)- NH₂; (SEQID NO: 292) Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)- NH₂; (SEQ IDNO: 292) Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO:292) Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 292)Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 293)H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; or (SEQ ID NO: 292)Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂;or pharmaceutically acceptable salts thereof.

In yet another preferred embodiment, the compound or compounds ofFormula (I), (II), (III), (IV), (V), (VI), (VII) or (VIII) as definedhereinabove, which are useful to treat insulin resistance in a mammaliansubject, with or without weight loss, or a pharmaceutically acceptablesalt thereof, are provided to said subject in need in a composition witha pharmaceutically acceptable carrier or diluent.

In preferred embodiment, the invention provides a method of treatinginsulin resistance in a subject in need thereof, comprising peripheraladministration of an effective amount of a melanocortin receptor δagonist to treat the insulin resistance in the subject in need thereof.

In one aspect, the melanocortin receptor δ agonist useful to treatinsulin resistance with or without an accompanying reduction in bodyweight in the subject in need thereof, is selected from the groupconsisting of:

SEQ ID NO: 1 Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 1Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 4Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH₂; SEQ ID NO: 5Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 11Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 12n-butanoyl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 13Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH₂; SEQ ID NO: 17n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 17n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH₂; SEQ ID NO: 61Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 19Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH₂; SEQ ID NO: 20Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH₂; SEQ ID NO: 21Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 22Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 22Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 23D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 25D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 27Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH₂; SEQ ID NO: 29Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEQ ID NO: 30Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 31Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 32Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 32Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 33Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 34Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 34Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 35Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 36Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 37Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 40Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 40Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 41Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; SEQ ID NO: 42Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; SEQ ID NO: 42Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; SEQ ID NO: 41Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; SEQ ID NO: 44Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; SEQ ID NO: 47Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 48Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; SEQ ID NO: 49Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; SEQ ID NO: 50Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 50Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 51Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 52Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 52Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 51Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 53Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 53Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 35Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 55Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 55Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH₂; SEQ ID NO: 56Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 56Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH₂; SEQ ID NO: 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 58Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH₂; (SEQ ID NO: 60)Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH₂;(SEQ ID NO: 61)Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH₂; (SEQ ID NO: 62)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 62)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 63)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 64)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)₂-Lys-Asp-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 65)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO66)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 67)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 68)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 69)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 69)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 70)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 72)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 73)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 74)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 75)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂; (SEQ ID NO: 76)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Gln-(Arg)₅-NH₂; (SEQ ID NO: 77)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)₅-NH₂; (SEQ ID NO: 78)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₄-Gln-Arg-NH₂; (SEQ ID NO: 79)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 80)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 80)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 84)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 85)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₃-Gln-(Arg)₂-NH₂; (SEQ ID NO: 86)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)₂-(Arg)₅-NH₂; (SEQ ID NO: 87)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₅-Gln-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 89)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 90)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 91)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 95)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 96)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 97)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 98)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 99)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 104)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 105)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 100)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 102)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 103)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 118)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 118)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 119)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 124)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 126)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 126)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 128)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 128)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 130)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 130)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 133)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 134)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 134)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 135)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 135)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 137)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂; (SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 139)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 140)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 143)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 144)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂;(SEQ ID NO: 148)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 148)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 149)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH_(2;);(SEQ ID NO: 149)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 151)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 151)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 152)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 152)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 154)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 153)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 154)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 155)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 155)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 157)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 156)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 156)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 157)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 158)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 158)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 159)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 160)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 161)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 162)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 164)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 163)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 163)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 164)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 165)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 165)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 166)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 166)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 168)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 167)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 167)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 168)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 170)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 169)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 169)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 170)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 171)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 171)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 173)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 172)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 172)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 173)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 175)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 176)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 177)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 178)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 179)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 180)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 181)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 182)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 183)Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 184)Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 183)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 185)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 186)Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 185)Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 186)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 187)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 189)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 190)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 189)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 190)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 191)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 191)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 193)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 194)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 193)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 194)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 195)Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 196)Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 197)Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 198)Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 199)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 199)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 201)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 202)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 203)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 203)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 204)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 204)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 207)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 206)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 206)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 207)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 208)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 208)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 209)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 210)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 209)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 211)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 212)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 213)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 213)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 267)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 214)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 216)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 214)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 217)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 215)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 216)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 215)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 217)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 220)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 224)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 225)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 224)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 225)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 226)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 229)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 230)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 232)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 231)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 232)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 233)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 234)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 235)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 236)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 235)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 236)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 237)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 238)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 237)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 238)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 239)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 240)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 239)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 240)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 241)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 242)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 241)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 242)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 243)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 243)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 245)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 246)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 245)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 246)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 247)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 247)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 249)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 250)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 249)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 250)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 251)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 251)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 253)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 254)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 253)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 254)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 255)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 255)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 257)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 258)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 257)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 258)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 259)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 260)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 259)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 260)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 261)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 262)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 261)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 262)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 263)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 264)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 263)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 264)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 265)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 266)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 265)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 266)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 268)Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 269) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂;(SEQ ID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 269) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂;(SEQ ID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 271) c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]NH₂; (SEQID NO: 271) c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 272)c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH₂; (SEQ ID NO:272) c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH₂; (SEQID NO: 273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]NH₂;(SEQ ID NO: 273)c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH₂; (SEQ ID NO:273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH₂; (SEQ IDNO: 273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH₂; (SEQID NO: 275) c[Hydantoin(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQID NO: 274) c[Hydantoin(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ IDNO: 274) c[Hydantoin(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin (C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]NH₂; (SEQ ID NO:275) c[Hydantoin-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH₂; (SEQ IDNO: 276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH₂; (SEQID NO: 276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH₂;(SEQ ID NO: 277) c[Hydantoin(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH₂;(SEQ ID NO: 278)Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 278) Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 278)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 279)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 281)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 281)Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 278)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 282)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 282)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 283)Hydantoin(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 283) Hydantoin(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 283)Hydantoin(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 284)Hydantoin(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 285)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 285)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 286)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 286)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 287)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 288)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 288)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 289)Hydantoin(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂,(SEQ ID NO: 290)c[Hydantoin(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 291) c[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 292) Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 292) Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 292) Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH₂; (SEQ ID NO:292) Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 292)Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 292)Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 293)H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; and (SEQ ID NO: 292)Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂;or a pharmaceutically acceptable salt thereof.

In one preferred aspect, the melanocortin receptor δ agonist useful totreat insulin resistance in the subject in need thereof, isAc-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO:50) or apharmaceutically acceptable salt thereof. In another preferred aspect,the melanocortin receptor δ agonist useful to treat insulin resistancein the subject in need thereof, isHydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ IDNO:278) or a pharmaceutically acceptable salt thereof.

In other aspects of the invention, administration of a compound orcomposition comprising a compound or pharmaceutical salt of a compoundof the invention useful to treat insulin resistance, is continuous,hourly, four times daily, three time daily, twice daily, once daily,once every other day, twice weekly, once weekly, once every two weeks,once a month, or once every two months, or longer.

The subject in need of treatment may be obese, overweight, of normalweight or lean. The obese, overweight, normal weight or lean subject maysuffer from type II diabetes. The preferred administration of a compoundor composition comprising a compound or pharmaceutical salt of acompound of the invention useful to treat insulin resistance, isperipheral administration. Examples of peripheral administration includeoral, subcutaneous, intraperitoneal, intramuscular, intravenous, rectal,transdermal or intranasal forms of administration.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1: Food consumed in fasted rats 6 hours after administration of 100nmole/Kg of selected compounds.

FIG. 2. Effect of subcutaneous administration of 75, 300 or 600nmole/kg/day of Compound A upon (A) body weight, (B) cumulative foodintake, (C) insulin levels and (D) glucose levels in rats.

FIG. 3. Effect of subcutaneous administration of 75, 300 or 600nmole/kg/day of Compound B upon (A) body weight, (B) cumulative foodintake, (C) insulin levels and (D) glucose levels in rats.

FIG. 4. Effect of subcutaneous administration of 200, 600 or 1800nmole/kg/day of Compound A upon blood glucose levels in mice.

FIG. 5. Effect of intraperitoneal administration of 6.4 μmole/kg ofCompound A upon blood glucose levels in obese mice.

DETAILED DESCRIPTION OF THE INVENTION

Recent studies have reported that staggering numbers of people worldwide are overweight and suffering a wide variety of serious andexpensive health problems. According the World Health Organization (asreported in Kouris-Blazos et al., Asia Pac. J. Clin. Nutr., 2007,16:329-338), an estimated 1 billion people throughout the world areoverweight and an estimated 300 million of these are obese. An estimated22 million children under the age of 5 are severely overweight and inthe European Union alone, the number of children who are overweight isexpected to rise by 1.3 million children per year (Kosti et al., 2006,Cent. Eur. J. Public Health, 14:151-159). Obesity, as defined by theStatistical Bulletin provided by the Metropolitan Life Insurance Co.,(1959, 40:1), is a condition in which a person is approximately 20-25%over normal body weight. Alternatively, an individual is consideredobese if the person has a body mass index of greater than 25% overnormal or greater than 30% over normal with risk factors (see Bray etal., Diabetes/Metabolism Review, 1988, 4:653-679 or Flynn et al., Proc.Nutritional Society, 1991, 50:413). One of the main causes for obesityis the consumption of a high caloric diet (Riccardi et al., Clin. Nutr.,2004, 23:447-456).

Diabetes is a chronic, debilitating disease afflicting many overweightand obese people. It is estimated that 20.8 million people in the UnitedStates alone have diabetes and more than 6 million more additional casesremain undiagnosed (Cornell, Manag. Care Pharm., 2007, 13:S11-5). Type 2diabetes (also referred to herein as type II diabetes) is a chronicdisease characterized by insulin resistance, impaired insulin secretionand hyperglycemia. Worldwide, type II diabetes is believed to affectapproximately 171 million people, imparting numerous microvascular andmacrovascular complications resulting in morbidity and mortality(Mudaliar, Indian J. Med. Res., 2007, 125:275-296). Mudaliar furthernotes that despite the availability of anti-hyperglycaemic agentsavailable, control of glucose remains elusive in many patients.

Insulin resistance, also referred to as reduced insulin sensitivity, isa condition in which the amount of insulin needed to clear glucose fromthe blood of a subject is increased as compared to the amount of insulinneeded to clear the same amount of glucose from the blood of a normal,non-insulin sensitive subject. Insulin resistance is regarded as themain link between obesity and type H diabetes (see Obici et al., J.Clin. Inv., 2001, 108:1079-1085 and references therein). It is knownthat rats fed a high fat diet show an increase in body weight(diet-induced obesity or DIO) and a decrease in insulin sensitivity.Such DIO rats provide an animal model in which to study the mechanismsof insulin resistance due to obesity (see for example Banno et al., FEBSletters, 2007, 581:1131-1136). The size and weight of adipose tissuesare increased in DIO rats and it is thought that the accompanyinghypertrophy of adipocytes leads to changes in the release ofadipocytokines such as leptin and adiponectin which are known toregulate insulin sensitivity; it is thought that morphological changesin adipose tissue as well as changes in plasma levels of adipocytokinesare among the causes of insulin resistance in DIO rats (summarized inBanno, et al., FEBS letters, 2007, 581:1131-1136 and referencestherein).

Melanocortins are proposed to play a large role in energy metabolism andhomeostasis. Melanocortins cleaved from the POMC precursor exert theireffects by binding to members of the melanocortin receptor familylocated in the brain. The major effect of melanocortin in the brain isto reduce food intake however, it has also been shown that melanocortinagonists or antagonists injected directly into the cerebral ventricleaffect insulin actions in the periphery while food was withdrawn orwhile food intake was kept constant (see Schwartz et al., Nature, 2000,404:661-671; Seeley et al., Ann. Rev. Nutr., 2004, 24:133-149; Cone etal., Recent Prog. Horm. Res., 1996, 51:287-317; Heijbor et al.,Diabetologia, 2005, 48:1621-1626; Obici et al., J. Clin. Inv., 2001,108:1079-1085). Taken together, these data suggest that centraladministration of melanocortins affects insulin sensitivity and may doso independently of energy balance. Banno et al., (FEBS letters, 2007,581:1131-1136) demonstrated that intracerebral injections of amelanocortin agonist to DIO rats ameliorated insulin sensitivity in theperiphery, decreased the size of and increased the number of adipocytesin white adipose tissue and decreased triglycerides content in theliver.

Considering the large numbers of overweight and/or insulin resistantsubjects in need of treatment, intracerebral administration is anunlikely means to disperse medicaments to patients. There is a need inthe art, therefore, to identify melanocortin agonists and antagonistssuitable for peripheral administration to affect parameters of insulinaction and energy metabolism such as insulin sensitivity, cellularcharacteristics of white adipose tissue, triglyceride levels and thelike.

Nomenclature and Abbreviations

As used herein, an “obese subject” or mammal is characterized as havinga body weight approximately 20% or greater than the normal body weightfor said subject. Normal body weight may be determined by a comparisonof the weight of the subject at a prior point in time, such as wheninsulin metabolism was normal, or by a comparison of the weight of thesubject as compared to averages of other subjects of a similar ageand/or condition.

As used herein, an “overweight subject” or mammal is characterized ashaving a body weight approximately 5% greater to approximately 20%greater than the normal body weight for said subject. Normal body weightmay be determined by a comparison of the weight of the subject at aprior point in time, such as when insulin metabolism was normal, or by acomparison of the weight of the subject as compared to averages of othersubjects of a similar age and/or condition.

As used herein, a “normal subject” or mammal is characterized as havinga body weight up to approximately 5% greater than to approximately 5%less than the normal body weight for said subject. Normal body weightmay be determined by a comparison of the weight of the subject at aprior point in time, such as when insulin metabolism was normal, or by acomparison of the weight of the subject as compared to averages of othersubjects of a similar age and/or condition.

As used herein, a “lean subject” or mammal is characterized as having abody weight approximately 5% to 30% or even to 50% less than the normalbody weight for said subject. Normal body weight may be determined by acomparison of the weight of the subject at a prior point in time, suchas when insulin metabolism was normal, or by a comparison of the weightof the subject as compared to averages of other subjects of a similarage and/or condition.

As used herein, the terms “treat”, “treating” and “treatment” includepalliative, curative and prophylactic treatment.

As used herein, “measurable” means the biologic effect is bothreproducible and significantly different from the baseline variabilityof the assay.

As used herein, peripherial administration includes all forms ofadministration of a compound or a composition comprising a compound ofthe instant invention which excludes intracranial administration.Examples of peripheral administration include, but are not limited to,oral, parenteral (e.g., intramuscular, intraperitoneal, intravenous orsubcutaneous injection, implant and the like), nasal, vaginal, rectal,sublingual or topical routes of administration, including transdermalpatch applications and the like.

A “subject”, as used herein and throughout this application, refers to amammalian or non-mammalian animal including, for example and withoutlimitation, a human, a rat, a mouse or farm animal. Reference to asubject does not necessarily indicate the presence of a disease ordisorder. The term “subject” includes, for example, a mammalian ornon-mammalian animal being dosed with a melanocortin analog as part ofan experiment, a mammalian or non-mammalian animal being treated to helpalleviate a disease or disorder, and a mammalian or non-mammalian animalbeing treated prophylactically to retard or prevent the onset of adisease or disorder. Subject mammals may be human subjects of any age,such as an infant, a child, an adult or an elderly adult.

A “therapeutically acceptable amount” of a compound or composition ofthe invention, regardless of the formulation or route of administration,is that amount which elicits a desired biological response in a subject.The biological effect of the therapeutic amount may occur at and bemeasured at many levels in an organism. For example, the biologicaleffect of the therapeutic amount may occur at and be measured at thecellular level by measuring the response at a receptor which bindsmelanocortin and/or a melanocortin analog, or the biological effect ofthe therapeutic amount may occur at and be measured at the system level,such as effecting an increase/decrease in the levels of insulin. Thebiological effect of the therapeutic amount may occur at and be measuredat the organism level, such as the alleviation of a symptom(s) orprogression of a disease or condition in a subject. A therapeuticallyacceptable amount of a compound or composition of the invention,regardless of the formulation or route of administration, may result inone or more biological responses in a subject. In the event that thecompound or composition of the invention is subject to testing in an invitro system, a therapeutically acceptable amount of the compound orcomposition may be viewed as that amount which gives a measurableresponse in the in vitro system of choice.

The nomenclature used to define the peptides is that typically used inthe art wherein the amino group at the N-terminus appears to the leftand the carboxyl group at the C-terminus appears to the right. Where theamino acid has D and L isomeric forms, it is the L form of the aminoacid that is represented unless otherwise explicitly indicated.

The compounds of the invention useful for the treatment of insulinresistance, with or without weight loss, may possess one or more chiralcenters and so exist in a number of stereoisomeric forms. Allstereoisomers and mixtures thereof are included in the scope of thepresent invention. Racemic compounds may either be separated usingpreparative HPLC and a column with a chiral stationary phase or resolvedto yield individual enantiomers utilizing methods known to those skilledin the art. In addition, chiral intermediate compounds may be resolvedand used to prepare chiral compounds of the invention.

The compounds of the invention useful for the treatment of insulinresistance, with or without weight loss, may exist in one or moretautomeric forms. All tautomers and mixtures thereof are included in thescope of the present invention.

For example, a claim to 2-hydroxypyridinyl would also cover itstautomeric form, α-pyridonyl.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Also, all publications, patentapplications, patents and other references mentioned herein areincorporated by reference in their entirety.

Symbol Meaning Abu α-aminobutyric acid Ac acyl group Acc1-amino-1-cyclo(C₃-C₉)alkyl carboxylic acid A3c1-amino-1-cyclopropanecarboxylic acid A4c1-amino-1-cyclobutanecarboxylic acid A5c1-amino-1-cyclopentanecarboxylic acid A6c1-amino-1-cyclohexanecarboxylic acid Aha 7-aminoheptanoic acid Ahx6-aminohexanoic acid Aib α-aminoisobutyric acid Aic2-aminoindan-2-carboxylic acid Ala or A alanine β-Ala β-alanine Apcdenotes the structure:

Apn 5-aminopentanoic acid (HN—(CH2)₄—C(O) Arg or R arginine hArghomoarginine Asn or N asparagine Asp or D aspartic acid Bal3-benzothienylalanine Bip 4,4′-biphenylalanine, represented by thestructure

Bpa 4-benzoylphenylalanine 4-Br—Phe 4-bromo-phenylalanine Chaβ-cyclohexylalanine hCha homo-cyclohexylalanine Chg cyclohexylglycineCys or C cysteine hCys homocysteine Dab 2,4-diaminobutyric acid Dap2,3-diaminopropionic acid Dip β,β-diphenylalanine Doc8-amino-3,6-dioxaoctanoic acid with the structure of:

2-Fua β-(2-furyl)-alanine Gaba 4-aminobutyric acid Gln or Q glutamineGlu or E glutamic acid Gly or G glycine His or H histidine 3-Hyptrans-3-hydroxy-L-proline, i.e., (2S,3S)-3-hydroxy-pyrrolidine-2-carboxylic acid 4-Hyp 4-hydroxyproline, i.e.,(2S,4R)-4-hydroxypyrrolidine-2- carboxylic acid Ile or I isoleucine Leuor L leucine hLeu homoleucine Lys or K lysine Met or M methionine β-hMetβ-homomethionine 1-Nal β-(1-naphthyl)alanine: 2-Nalβ-(2-naphthyl)alanine Nip nipecotic acid Nle norleucine Oicoctahydroindole-2-carboxylic acid Orn ornithine 2-Palβ-(2-pyridiyl)alanine 3-Pal β-(3-pyridiyl)alanine 4-Palβ-(4-pyridiyl)alanine Pen penicillamine Pff (S)-pentafluorophenylalaninePhe or F phenylalanine hPhe homophenylalanine Pro or P proline hProhomoproline Ser or S serine Tle tert-Leucine Taz β-(4-thiazolyl)alanine2-Thi β-(2-thienyl)alanine 3-Thi β-(3-thienyl)alanine Thr or T threonineTrp or W tryptophan Tyr or Y tyrosine D-(Et)Tyr has a structure of

Val or V valine Certain other abbreviations used herein are defined asfollows: Boc: tert-butyloxycarbonyl Bzl: benzyl DCM: dichloromethaneDIC: N,N-diisopropylcarbodiimide DIEA: diisopropylethyl amine Dmab:4-{N-(1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-3-methylbutyl)-amino}benzyl DMAP: 4-(dimethylamino)pyridine DMFdimethylformamide DNP: 2,4-dinitrophenyl Fm: fluorenylmethyl Fmoc:fluorenylmethyloxycarbonyl For: formyl HBTU:2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphatecHex cyclohexyl HOAT:O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate HOBt: 1-hydroxy-benzotriazole MBNA4-methylbenzhydrylamine Mmt: 4-methoxytrityl NMP: N-methylpyrrolidoneO—tBu oxy-tert-butyl Pbf:2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl PyBroPbromo-tris-pyrrolidino-phosphonium hexafluorophosphate tBu: tert-butylTIS: triisopropylsilane TOS: tosyl Trt trityl TFA: trifluoro acetic acidTFFH: tetramethylfluoroforamidinium hexafluorophosphate Z:benzyloxycarbonyl

Unless otherwise indicated, with the exception of the N-terminal aminoacid, all abbreviations (e.g. Ala) of amino acids in this disclosurestand for the structure of —NH—C(R)(R′)—CO—, wherein R and R′ each is,independently, hydrogen or the side chain of an amino acid (e.g., R═CH₃and R′═H for Ala), or R and R′ may be joined to form a ring system.

For the N-terminal amino acid, the abbreviation stands for the structureof:

The designation “NH₂” in e.g.,Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO:7), indicatesthat the C-terminus of the peptide is amidated.Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) (SEQ ID NO:36), oralternatively Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH (SEQ IDNO:36), indicates that the C-terminus is the free acid.

“-c(Cys-Cys)-” or “-cyclo(Cys-Cys)-” denotes the structure:

“-c(Cys-Pen)-” or “-cyclo(Cys-Pen)-” denotes the structure:

“-c(Asp-Lys)-” or “-cyclo(Asp-Lys)-” denotes the structure:

Applicants have devised the following shorthand used in naming thespecific embodiments and/or species:

“HydantoinC(O)-(A^(a)-A^(b))” denotes the structure:

wherein amino acid “A^(a)” has the structure:

and

amino acid “A^(b)” the structure:

For example, a compound represented as“c[Hydantoin(C(O)-(Cys-Ab))-A¹-A²-A³-A⁴-Cys]-” would have the followingthe structure:

whereas a compound represented as“c[Hydantoin(C(O)-(A^(b)-Cys))-A¹-A²-A³-A⁴-Cys]-” would have thestructure:

For further guidance, “c[Hydantoin(C(O)-(Asp-A^(b)))-A¹-A²-A³-A⁴-Lys]-”represents the following compound:

whereas “c[Hydantoin(C(O)-(Dap-Ab))-A¹-A²-A³-A⁴-Asp]-” has the followingformula:

“Acyl” refers to R″—C(O)—, where R″ is H, alkyl, substituted alkyl,heteroalkyl, substituted heteroalkyl, alkenyl, substituted alkenyl,aryl, alkylaryl, or substituted alklyaryl, and is indicated in thegeneral formula of a particular embodiment as “Ac”.

“Alkyl” refers to a hydrocarbon group containing one or more carbonatoms, where multiple carbon atoms if present are joined by singlebonds. The alkyl hydrocarbon group may be straight-chain or contain oneor more branches or cyclic groups.

“Hydroxyalkyl” refers to an alkyl group wherein one or more hydrogenatoms of the hydrocarbon group are substituted with one or more hydroxyradicals, such as hydroxymethyl, hydroxyethyl, hydroxypropyl,hydroxybutyl, hydroxypentyl, hydroxyhexyl and the like.

“Substituted alkyl” refers to an alkyl wherein one or more hydrogenatoms of the hydrocarbon group are replaced with one or moresubstituents selected from the group consisting of halogen, (i.e.,fluorine, chlorine, bromine, and iodine), —OH, —CN, —SH, —NH₂, —NHCH₃,—NO₂, and —C₁₋₂₀ alkyl, wherein said —C₁₋₂₀ alkyl optionally may besubstituted with one or more substituents selected, independently foreach occurrence, from the group consisting of halogens, —CF₃, —OCH₃,—OCF₃, and —(CH₂)₀₋₂₀—COOH. In different embodiments 1, 2, 3 or 4substituents are present. The presence of —(CH₂)₀₋₂₀—COOH results in theproduction of an alkyl acid. Non-limiting examples of alkyl acidscontaining, or consisting of, —(CH₂)₀₋₂₀—COOH include 2-norbornaneacetic acid, tert-butyric acid, 3-cyclopentyl propionic acid, and thelike.

The term “halo” encompasses fluoro, chloro, bromo and iodo.

“Heteroalkyl” refers to an alkyl wherein one of more of the carbon atomsin the hydrocarbon group is replaced with one or more of the followinggroups: amino, amido, —O—, —S— or carbonyl. In different embodiments 1or 2 heteroatoms are present.

“Substituted heteroalkyl” refers to a heteroalkyl wherein one or morehydrogen atoms of the hydrocarbon group are replaced with one or moresubstituents selected from the group consisting of halogen, (i.e.,fluorine, chlorine, bromine, and iodine), —OH, —CN, —SH, —NH₂, —NHCH₃,—NO₂, and —C₁₋₂₀ alkyl, wherein said —C₁₋₂₀ alkyl optionally may besubstituted with one or more substituents selected, independently foreach occurrence, from the group consisting of halogens, —CF₃, —OCH₃,—OCF₃, and —(CH₂)₀₋₂₀—COOH. In different embodiments 1, 2, 3 or 4substituents are present.

“Alkenyl” refers to a hydrocarbon group made up of two or more carbonswhere one or more carbon-carbon double bonds are present. The alkenylhydrocarbon group may be straight-chain or contain one or more branchesor cyclic groups.

“Substituted alkenyl” refers to an alkenyl wherein one or more hydrogensare replaced with one or more substituents selected from the groupconsisting of halogen (i.e., fluorine, chlorine, bromine, and iodine),—OH, —CN, —SH, —NH₂, —NHCH₃, —NO₂, and —C₁₋₂₀ alkyl, wherein said —C₁₋₂₀alkyl optionally may be substituted with one or more substituentsselected, independently for each occurrence, from the group consistingof halogens, —CF₃, —OCH₃, —OCF₃, and —(CH₂)₀₋₂₀—COOH. In differentembodiments 1, 2, 3 or 4 substituents are present.

“Aryl” refers to an optionally substituted aromatic group with at leastone ring having a conjugated pi-electron system, containing up to threeconjugated or fused ring systems. Aryl includes carbocyclic aryl,heterocyclic aryl and biaryl groups. Preferably, the aryl is a 5- or6-membered ring. Preferred atoms for a heterocyclic aryl are one or moresulfur, oxygen, and/or nitrogen. Non-limiting examples of aryl includephenyl, 1-naphthyl, 2-naphthyl, indole, quinoline, 2-imidazole,9-anthracene, and the like. Aryl substituents are selected from thegroup consisting of —C₁-20 alkyl, —C₁₋₂₀ alkoxy, halogen (i.e.,fluorine, chlorine, bromine, and iodine), —OH, —CN, —SH, —NH₂, —NO₂,—C₁₋₂₀ alkyl substituted with halogens, —CF₃, —OCF₃, and—(CH₂)₀₋₂₀—COOH. In different embodiments the aryl contains 0, 1, 2, 3,or 4 substituents.

“Alkylaryl” refers to an “alkyl” joined to an “aryl”.

The term “(C₁-02)hydrocarbon moiety” encompasses alkyl, alkenyl andalkynyl and in the case of alkenyl and alkynyl there is C₂-C₁₂.

For the avoidance of doubt, unless otherwise indicated, the termsubstituted means substituted by one or more defined groups. In the casewhere groups may be selected from a number of alternative groups, theselected groups may be the same or different. For the avoidance ofdoubt, the term independently means that where more than one substituentis selected from a number of possible substituents, those substituentsmay be the same or different.

The pharmaceutically acceptable salts of the compounds of the inventionwhich contain a basic centre are, for example, non-toxic acid additionsalts formed with inorganic acids such as hydrochloric, hydrobromic,hydroiodic, sulfuric and phosphoric acid, with carboxylic acids or withorgano-sulfonic acids. Examples include the HCl, HBr, HI, sulfate orbisulfate, nitrate, phosphate or hydrogen phosphate, acetate, benzoate,succinate, saccharate, fumarate, maleate, lactate, citrate, tartrate,gluconate, camsylate, methanesulfonate, ethanesulfonate,benzenesulfonate, p-toluenesulfonate and pamoate salts. Compounds of theinvention can also provide pharmaceutically acceptable metal salts, inparticular non-toxic alkali and alkaline earth metal salts, with bases.Examples include the sodium, potassium, aluminum, calcium, magnesium,zinc and diethanolamine salts (Berge, S. M. et al., J. Pharm. Sci.,66:1-19 (1977); Gould, P. L., Int'l J. Pharmaceutics, 33:201-17 (1986);and Bighley, L. D. et al., Encyclo. Pharma. Tech., Marcel Dekker Inc,New York, 13:453-97 (1996).

The pharmaceutically acceptable solvates of the compounds of theinvention include the hydrates thereof. Also included within the scopeof the invention and various salts of the invention are polymorphsthereof. Hereinafter, compounds their pharmaceutically acceptable salts,their solvates or polymorphs, defined in any aspect of the invention(except intermediate compounds in chemical processes) are referred to as“compounds of the invention”.

In Vitro Studies

Compounds of the present invention can be and were tested for activityas ligands of one or more of the melanocortin receptors according to thefollowing procedures. One skilled in the art would know that proceduressimilar to those described herein may be used to assay the bindingactivities of the compounds of the invention to melanocortin receptormolecules.

Radioligand Binding Assays

Cellular membranes used for the in vitro receptor binding assays wereobtained from transgenic CHO-K1 cells stably expressing hMC-R receptorsubtypes 1, 3, 4 or 5. The CHO-K1 cells expressing the desired hMC-Rreceptor type were sonicated (Branson® setting 7, approximately 30 sec)in ice-cold 50 mM Tris-HCl at pH 7.4 and then centrifuged at 39,000 gfor 10 minutes at approximately 4° C. The pellets were resuspended inthe same buffer and centrifuged at 50,000 g for 10 minutes atapproximately 4° C. The washed pellets containing the cellular membraneswere stored at approximately −80° C.

Competitive inhibition of [¹²⁵I](Tyr²)-(Nle⁴-D-Phe⁷)α-MSH([¹²⁵I]-NDP-α-MSH, Amersham Biosciences®) binding was carried out inpolypropylene 96 well plates. Cell membranes (1-10 μg protein/well)prepared as described above were incubated in 50 mM Tris-HCl at pH 7.4containing 0.2% bovine serum albumin (BSA), 5 mM MgCl₂, 1 mM CaCl₂ and0.1 mg/mL bacitracin, with increasing concentrations of the testcompound and 0.1-0.3 nM [¹²⁵I]-NDP-α-MSH for approximately 90-120minutes at approximately 37° C. Bound [¹²⁵I]-NDP-α-MSH ligand wasseparated from free [¹²⁵I]-NDP-α-MSH by filtration through GF/C glassfiber filter plates (Unifilter®; Packard) presoaked with 0.1% (w/v)polyethylenimine (PEI), using a Packard Filtermate® harvester. Filterswere washed three times with 50 mM Tris-HCl at pH 7.4 at a temperatureof approximately 0-4° C. and then assayed for radioactivity using aPackard Topcount® scintillation counter. Binding data were analyzed bycomputer-assisted non-linear regression analysis (XL fit; IDBS). Aselection of the preferred embodiments was tested using theabove-discussed assay and the binding constants (Ki in nM) are reportedin Tables 5, 6, 7 and 8.

TABLE 5 Radioligand Binding Assay Data for Selected Compounds Table 5AKi Ki Ki Ki Ki hMC1-R/ SEQ ID Compound hMC1-R hMC3-R hMC4-R hMC5-R MC4-RNO: Ac-Arg-c(Cys-D-Ala-His-D- 3.87 10.1 2.09 430 1.9 SEQ IDPhe-Arg-Trp-Cys)-NH₂ NO: 50 Ac-D-Arg-c(Cys-D-Ala-His- 4.01 12.1 1.76 3522.3 SEQ ID D-Phe-Arg-Trp-Cys)-NH₂ NO: 50 Ac-D-Arg-c(Cys-D-Ala-His- 8.2913.3 2.78 816 3.0 SEQ ID D-Phe-Arg-Trp-Pen)-NH₂ NO: 51Ac-D-Arg-c(Cys-His-D-Phe- 3.93 172 11.0 538 0.36 SEQ IDArg-Trp-Gaba-Pen)-NH₂ NO: 52 Ac-Arg-c(Cys-His-D-Phe- 1.81 20.5 4.57 5020.4 SEQ ID Arg-Trp-Gaba-Pen)-NH₂ NO: 52 Ac-Arg-c(Cys-D-Ala-His-D- 9.6722.0 4.2 1900 2.3 SEQ ID Phe-Arg-Trp-Pen)-NH₂ NO: 51Ac-D-Arg-c(Asp-His-D- 0.79 45.5 1.21 493 0.6 SEQ IDPhe-Arg-Trp-Ala-Lys)-NH₂ NO: 53 Ac-Arg-c(Asp-His-D-Phe- 0.68 20.7 1.01783 0.7 SEQ ID Arg-Trp-Ala-Lys)-NH₂ NO: 53 Table 5B Ki Ki Ki Ki KihMC1-R/ SEQ ID Compound hMC1-R hMC3-R hMC4-R hMC5-R MC4-R NO:Ac-Nle-c(Cys-D-Ala-His-D- 114 63.9 3.07 1657 37.1 SEQ ID2-Nal-Arg-1-Nal-Cys)-NH₂ NO: 16 Ac-Nle-c(Cys-D-Ala-His-D- 11 26 7.6 18001.4 SEQ ID Phe-Arg-Trp-Cys)-NH₂ NO: 7 D-Phe-c(Cys-His-D-(Et)Tyr- 0.059.3 1.1 2.9 0.0 SEQ ID Arg-Trp-β-Ala-D-Cys)-Thr- NO: 24 NH₂Nle-c(Cys-His-D-Phe-Arg- 0.07 4.1 0.85 8.8 0.1 SEQ ID Trp-Apn-Cys)-NH₂NO: 27 Ac-Nle-c(Cys-His-D-Phe- 0.12 10 0.43 0.42 0.3 SEQ IDArg-Trp-Gaba-Pen)-NH₂ NO: 32 Nle-c(Cys-His-D-Phe-Arg- 0.05 1.3 0.47 0.20.1 SEQ ID Trp-Gaba-Cys)-NH₂ NO: 34 Ac-Nle-c(Asp-His-D-Phe- 0.0996 93180.617 10.9 0.16 SEQ ID Arg-Trp-β-Ala-Lys)-NH₂ NO: 1Ac-Nle-c(Cys-His-D-Phe- .0132 16.1 1.23 0.359 0.11 SEQ IDArg-Trp-Ahx-Cys)-NH₂ NO: 2 D-Phe-c(Cys-His-D-Phe- 0.207 43.2 2.58 3440.08 SEQ ID Arg-Trp-β-Ala-D-Cys)-Thr- NO: 3 NH₂ D-Phe-c(Cys-His-D-Phe-0.420 106 4.75 1260 0.09 SEQ ID Arg-Trp-Gaba-D-Cys)-Thr- NO: 3 NH₂Ac-Nle-c(Cys-His-D-Phe- 0.0951 9.33 0.894 13.4 0.11 SEQ IDArg-Trp-Apn-Cys)-NH₂ NO: 2 Ac-Nle-c(Asp-His-D-Phe- 0.999 300 11.1 4310.09 SEQ ID Arg-Trp-Apn-Lys)-NH₂ NO: 4 Ac-Cha-c(Asp-His-D-Phe- 0.10611.8 1.49 110 0.07 SEQ ID Arg-Trp-Gaba-Lys)-NH₂ NO: 6Ac-Nle-c(Asp-His-D-Phe- 0.0506 9.89 1.04 16.3 0.05 SEQ IDArg-Trp-Gaba-Lys)-NH₂ NO: 6 Ac-Chg-c(Asp-His-D-Phe- 0.884 223 22.5 6090.04 SEQ ID Arg-Trp-Gaba-Lys)-NH₂ NO: 11 Ac-hCha-c(Asp-His-D-Phe- 0.72193.5 56.0 747 0.01 SEQ ID Arg-Trp-Gaba-Lys)-NH₂ NO: 11Ac-D-Chg-c(Asp-His-D- 0.227 14.5 2.99 164 0.08 SEQ IDPhe-Arg-Trp-Gaba-Lys)- NO: 11 NH₂ Ac-hPhe-c(Asp-His-D-Phe- 0.277 25.23.37 203 0.08 SEQ ID Arg-Trp-Gaba-Lys)-NH₂ NO: 11Ac-Nle-c(Cys-His-D-Phe- 0.323 14.1 1.96 24.0 0.16 SEQ IDArg-D-Trp-β-Ala-Cys)-NH₂ NO: 15 Ac-Nle-c(Pen-D-Ala-His-D- 34.1 118 17.05560 2.01 SEQ ID Phe-Arg-Trp-Cys)-NH₂ NO: 21 Ac-Nle-c(Cys-D-Ala-His-D-29.1 22.8 3.84 2550 7.58 SEQ ID Phe-Arg-Trp-Pen)-NH₂ NO: 22D-Phe-c(Cys-His-D-Phe- 0.442 123 10.3 521 0.04 SEQ IDhArg-Trp-β-Ala-D-Cys)- NO: 23 Thr-NH₂ D-Phe-c(Cys-His-D-Phe- 5.80 3370583 1130 0.01 SEQ ID Arg-Bip-β-Ala-D-Cys)-Thr- NO: 25 NH₂D-Phe-c(Cys-His-D-(Et)Tyr- 0.0567 31.4 14.7 9.27 0 SEQ IDhArg-Trp-β-Ala-D-Cys)- NO: 24 Thr-NH₂ D-Phe-c(Cys-His-D-Phe- 1.68 1260172 1220 0.01 SEQ ID hArg-Bip-β-Ala-D-Cys)- NO: 26 Thr-NH₂D-Phe-c(Cys-His-D-(Et)Tyr- 0.128 85.6 36.9 38.0 0 SEQ IDhArg-Bip-β-Ala-D-Cys)- NO: 26 Thr-NH₂ Ac-Nle-c(Cys-D-Ala-His-D- 0.352149 3.01 339 0.12 SEQ ID Phe-Arg-Trp-Gly-Cys)-NH₂ NO: 54Ac-Nle-c(Cys-D-Ala-His-D- 3.93 876 48.0 4940 0.08 SEQ IDPhe-Arg-Trp-D-Ala-Cys)- NO: 54 NH₂ Ac-Nle-c(Cys-D-Ala-His-D- 0.995 2874.80 766 0.21 SEQ ID Phe-Arg-Trp-β-Ala-Cys)- NO: 54 NH₂Ac-Nle-c(Cys-D-Ala-His-D- 0.848 184 3.76 956 0.23 SEQ IDPhe-Arg-Trp-Gaba-Cys)- NO: 54 NH₂ Ac-Nle-c(Cys-D-Ala-His-D- 1.10 2287.58 859 0.15 SEQ ID Phe-Arg-Trp-Apn-Cys)- NO: 54 NH₂Ac-Nle-c(Asp-D-Ala-His-D- 0.659 98.9 2.55 4.19 0.26 SEQ IDPhe-Arg-Trp-Lys)-NH₂ NO: 28 Ac-Nle-c(Asp-D-Ala-His-D- 4.12 445 50.6 43000.08 SEQ ID Phe-Arg-Bal-Lys)-NH₂ NO: 28 Ac-c(Cys-Glu-His-D-Phe- 111 171047.7 694 2.33 SEQ ID Arg-Trp-Ala-Cys)-NH₂ NO: 55 Ac-c(Cys-Glu-His-D-Phe-262 2500 96.4 1460 2.72 SEQ ID Arg-2-Nal-Ala-Cys)-NH₂ NO: 55Ac-c(Cys-D-Ala-His-D-Phe- 199 5990 96.7 >10000 2.06 SEQ IDArg-Trp-Ala-Cys)-NH₂ NO: 56 Ac-c(Cys-D-Ala-His-D-Phe- 132 4560 40.7 88103.24 SEQ ID Arg-2-Nal-Ala-Cys)-NH₂ NO: 56 Ac-Nle-c(Cys-D-Ala-His-D- 9.121130 22.1 2860 0.41 SEQ ID Phe-Arg-Trp-Ala-Cys)-NH₂ NO: 57Ac-Nle-c(Cys-D-Ala-His-D- 1.00 227 5.55 496 0.18 SEQ IDPhe-Arg-Trp-β-Ala-Cys)- NO: 57 NH₂ Ac-Nle-c(Cys-D-Ala-His-D- 0.536 1693.12 358 0.17 SEQ ID Phe-Arg-Trp-Gaba-Cys)- NO: 57 NH₂Ac-Nle-c(Cys-D-Ala-His-D- 32.1 330 17.4 165 1.84 SEQ IDPhe-Arg-Trp-Pen)-OH NO: 29 Ac-Nle-c(Cys-D-Abu-His- 10.6 41.1 7.69 54.91.38 SEQ ID D-Phe-Arg-Trp-Cys)-NH₂ NO: 30 Ac-Nle-c(Cys-D-Val-His-D- 13.0104 10.1 40 1.29 SEQ ID Phe-Arg-Trp-Cys)-NH₂ NO: 30Ac-Nle-c(Cys-D-Ile-His-D- 4.28 38.5 9.0 12.5 0.48 SEQ IDPhe-Arg-Trp-Cys)-NH₂ NO: 30 Ac-Nle-c(Cys-D-Leu-His-D- 1.60 6.82 4.135.57 0.39 SEQ ID Phe-Arg-Trp-Cys)-NH₂ NO: 30 Ac-Nle-c(Cys-D-Tle-His-D-12.0 85.8 11.2 40 1.07 SEQ ID Phe-Arg-Trp-Cys)-NH₂ NO: 30Ac-Nle-c(Cys-D-Cha-His-D- 0.353 2.08 1.41 0.857 0.25 SEQ IDPhe-Arg-Trp-Cys)-NH₂ NO: 30 Ac-Nle-c(Pen-His-D-Phe- 0.537 86.1 5.89 2.560.09 SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 31 Ac-Nle-c(Pen-His-D-Phe- 0.744178 3.51 2.69 0.21 SEQ ID Arg-Trp-Gaba-Pen)-NH₂ NO: 32Ac-Leu-c(Cys-His-D-Phe- 0.216 17.4 0.995 0.486 0.22 SEQ IDArg-Trp-Gaba-Cys)-NH₂ NO: 33 Ac-Cha-c(Cys-His-D-Phe- 0.107 9.11 0.8840.354 0.12 SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 33 Ac-Ile-c(Cys-His-D-Phe-0.148 13.9 1.06 0.423 0.14 SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 33Ac-Phe-c(Cys-His-D-Phe- 0.254 18.5 2.13 0.714 0.12 SEQ IDArg-Trp-Gaba-Cys)-NH₂ NO: 33 Ac-Val-c(Cys-His-D-Phe- 0.256 29.9 1.980.864 0.13 SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 33 Ac-2-Nal-c(Cys-His-D-Phe-0.560 39.2 2.94 2.73 0.19 SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 33Phe-c(Cys-His-D-Phe-Arg- 0.186 15.2 4.93 0.537 0.04 SEQ IDTrp-Gaba-Cys)-NH₂ NO: 34 Ac-Nle-c(Cys-3-Pal-D-Phe- 21.1 151 10.4 92.62.03 SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 35 Ac-Nle-c(Cys-D-Ala-His-D- 30.7152 15.6 114 1.97 SEQ ID Phe-Arg-Trp-Cys)-OH NO: 36Ac-Nle-c(Cys-His-Phe-Arg- 5.20 150 138 20.3 0.04 SEQ IDD-Trp-Gaba-Cys)-NH₂ NO: 37 Ac-Nle-c(Asp-D-Ala-His-D- 4.89 290 21.3 11.10.23 SEQ ID Phe-Arg-Bal-Ala-Lys)-NH₂ NO: 58 Ac-Nle-c(Cys-D-Ala-His-D-25.5 3.82 7.61 102 3.35 SEQ ID 2-Nal-Arg-Trp-Cys)-NH₂ NO: 16Ac-Nle-c(Cys-D-Ala-His-D- 32.5 5.85 2.53 94.6 12.85 SEQ ID2-Nal-Arg-2-Nal-Cys)-NH₂ NO: 16 Ac-Nle-c(Cys-D-Ala-His-D- 22.2 12.7 16.6125 1.34 SEQ ID 2-Nal-Arg-Bal-Cys)-NH₂ NO: 20 Ac-Nle-c(Asp-His-D-2-Nal-1.17 1.56 0.277 3.24 4.22 SEQ ID Arg-Trp-Ala-Lys)-NH₂ NO: 38Ac-Nle-c(Asp-His-D-2-Nal- 0.648 2.78 0.329 1.4 1.97 SEQ IDArg-Trp-β-Ala-Lys)-NH₂ NO: 38 Ac-Nle-c(Cys-His-D-2-Nal- 0.393 1.86 0.3751.11 1.05 SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 39 Ac-Nle-c(Cys-His-D-2-Nal-0.333 2.91 0.998 0.366 0.33 SEQ ID Arg-Trp-Ahx-Cys)-NH₂ NO: 39Ac-hPhe-c(Asp-His-D-2- 0.461 2.45 0.931 1.37 0.50 SEQ IDNal-Arg-Trp-Gaba-Lys)- NO: 40 NH₂ Ac-Cha-c(Asp-His-D-2-Nal- 0.576 3.982.82 3.91 0.20 SEQ ID Arg-Trp-Gaba-Lys)-NH₂ NO: 40 Table 5C Ki Ki Ki KiKi hMC1-R/ SEQ ID Compound hMC1-R hMC3-R hMC4-R hMC5-R MC4-R NO:Ac-Arg-c(Cys-D-Ala-His-D- 17.9 1.68 0.256 23.4 69.9 SEQ ID2-Nal-Arg-Trp-Cys)-NH₂ NO: 49

TABLE 6 Radioligand Binding Assay Data for Selected Compounds Table 6AKi Ki Ki Ki Compound hMC1-R hMC3-R hMC4-R hMC5-RAc-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 49.9 9.00 0.569 218Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269)Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg- 11.9 38.1 5.70 11.8Arg-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- NH₂ (SEQ ID NO: 60)Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg- 3.46 16.6 6.65 4.88Arg-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp- Lys)-NH₂ (SEQ ID NO: 61)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala- 0.614 5.09 2.31 3.23Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg- Arg-NH₂ (SEQ ID NO: 62)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β- 1.56 14.1 5.17 7.12Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg- Arg-Arg-NH₂ (SEQ ID NO: 62)H-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-Doc- 1.10 1.58 6.00 0.629Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg- Arg-Arg-NH₂ (SEQ ID NO: 63)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- 0.0868 0.751 0.0944 0.147Pro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys-Lys-Arg- Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ IDNO: 64) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly- 1.66 4.80 0.250 9.62Cys)-Pro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys-Lys- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 65) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β- 0.0452 0.2980.169 0.386 Ala-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 66) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- 0.0808 0.3960.0747 0.311 Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 67)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly- 4.41 4.23 0.455 12.9Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 68)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 1.25 0.661 0.292 5.94Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 1.89 0.546 0.166 6.06Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 87.8 9.08 1.20 359Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 124 17.8 1.11 348Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 163 23.0 0.586 844Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- 0.144 0.352 0.0845 0.415Doc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO:701) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 1.74 0.590 0.170 4.38Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 3.86 4.97 0.192 38.3Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg- Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ IDNO: 83) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 12.8 15.9 0.950 165Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 73) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 3.07 4.05 0.49831.1 Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 74)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 0.792 0.570 0.162 4.18Cys)-Pro-Pro-Lys-Asp-βAla-Tyr-Gly-Arg-Lys-Lys-Arg-Gln-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 75)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 0.726 0.474 0.209 5.12Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Gln-Arg-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 76)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 0.857 0.580 0.209 4.42Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-Arg-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 77)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 0.813 0.675 0.269 4.20Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Arg-Gln-Arg-NH₂ (SEQ ID NO: 78)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 7.84 10.2 0.783 91.8Pro-Pro-Lys-Asp-β-Ala-Tyr-Aib-Arg-Lys- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 79) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 2.93 9.07 0.29359.0 Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 80) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 2.42 6.56 0.23841.7 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 80) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 6.66 19.3 0.81988.8 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 2.63 2.09 0.0737 11.6Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 82) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 2.48 1.21 0.209 9.17Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 82) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 3.65 2.26 0.261 12.1Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 81) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 7.32 11.00.659 78.0 Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 4.11 7.26 0.302 48.3Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg- Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ IDNO: 84) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 6.77 14.3 0.781 84.0Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQID NO: 283) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 3.04 3.22 0.230 3.85Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Gln-Arg-Arg-NH₂ (SEQ ID NO: 2685)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 3.24 2.66 0.208 5.96Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-Lys-Lys-Arg-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 86)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 1.58 1.43 0.275 2.97Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Arg-Arg-Gln-NH₂ (SEQ ID NO: 87)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 4.59 6.28 0.588 22.6Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 6.46 5.22 0.380 15.3Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 71) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 4.62 5.68 0.50545.3 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 88) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 2.12 3.99 0.35227.5 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 89) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 3.41 0.975 0.54911.3 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 88) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 4.18 1.12 0.22315.3 Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 90)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 2.71 0.732 0.202 5.53Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 91) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 5.66 1.40 0.4466.23 Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 92)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.211 0.665 0.635 118Cys)-(Doc)2-Tyr-Gly-Arg-Lys-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO:136) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.351 0.891 0.503 102Cys)-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Gln- Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO:137) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.209 0.699 0.596 137Cys)-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂(SEQ ID NO:136) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.439 1.52 0.476 115Cys)-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln- Arg-Arg-Arg-NH₂(SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.821 2.50 0.700 148Cys)-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg- Arg-Arg-NH₂(SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.406 1.11 0.602 131Cys)-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO:139) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 1.27 4.63 1.51 220Cys)-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln- Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO:139) Table 6B Ki Ki Ki Ki Compound hMC1-R hMC3-R hMC4-R hMC5-RAc-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala- 2058 113 10.7 239Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib- 1818 306 5.87 979Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 1.75 1.74 0.15 16.8Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 95)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 1.50 1.61 0.301 10.4Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 96)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 1.81 2.08 0.305 19.3Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 97) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 2.69 2.59 0.24319.2 Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 2.25 0.62 0.303 2.77Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 99) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 1.49 0.604 0.865 3.13Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg- Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 101) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 3.28 1.950.575 15.5 Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 105)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 2.24 1.57 0.437 16.4Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 100) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 2.14 1.120.624 11.9 Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 2.50 1.59 0.573 15.7Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg-Lys- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 102) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 3.00 1.70 0.44215.5 Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg- Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 104) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)- 4.29 2.15 0.42515.5 Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 103) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.410 0.837 0.24656.3 Cys)-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ IDNO: 141) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.572 1.07 0.210 63.6Cys)-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO:142) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.475 0.800 0.196 53.8Cys)-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.779 1.21 0.293 56.0Cys)-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.212 1.23 0.484 58.5Cys)-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg- Arg-Arg-NH₂ (SEQ ID NO: 143)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.778 1.22 0.468 47.0Cys)-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln-Arg- Arg-Arg-NH₂ (SEQ ID NO: 144)

TABLE 7 Binding Constants for Formula (V) Examples Table 7A Ki Ki Ki KiFormula (V) Compounds hMC1 hMC3 hMC4 hMC5c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe- 230 7590 126 7020Arg-Trp-Cys]-NH₂ (SEQ ID NO: 271)c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- 72.6 1920 45.2 >10000Arg-Trp-Lys]-NH₂ (SEQ ID NO: 276)c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- 60.4 2840 52.4 >10000Arg-Trp-Orn]-NH₂ (SEQ ID NO: 276)c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- 28 90.5 12.7 877Arg-Trp-Dab]-NH₂ (SEQ ID NO: 276)c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- 16.4 863 4.97 >10000Arg-Trp-Dap]-NH₂ (SEQ ID NO: 276)c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe- 37.7 576 7.81 6400Arg-Trp-Orn]-NH₂ (SEQ ID NO: 273)c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe- 66.6 1820 19.9 >10000Arg-Trp-Dap]-NH₂ (SEQ ID NO: 273)c[Hydantoin(C(O)-(Asp-His))-D-2-Nal-Arg- 200 68.8 6.63 142 Trp-Lys]-NH₂(SEQ ID NO: 275) c[Hydantoin(C(O)-(Asp-Aic))-D-2-Nal-Arg- 9028 2628 35.81156 Trp-Lys]-NH₂ (SEQ ID NO: 275)c[Hydantoin(C(O)-(Asp-A5c))-D-2-Nal-Arg- 9938 2390 44.6 1103Trp-Lys]-NH₂ (SEQ ID NO: 275) c[Hydantoin(C(O)-(Asp-A6c))-D-2-Nal-Arg-2170 1479 16.5 451 Trp-Lys]-NH₂ (SEQ ID NO: 275)c[Hydantoin(C(O)-(Asp-Apc))-D-2-Nal-Arg- 1276 2756 266 1096 Trp-Lys]-NH₂(SEQ ID NO: 275) c[Hydantoin(C(O)-(Asp-A3c))-D-2-Nal-Arg- 7567 1922 4202879 Trp-Lys]-NH₂ (SEQ ID NO: 275) TABLE 7B - Binding Constants forFormula (VI) Examples Ki Ki Ki Ki Formula (VI) Compounds hMC1 hMC3 hMC4hMC5 Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D- 14.3 198 5.76 67.8Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D- 11.9 311 5.41 73.9Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(A6c-Nle))-c(Cys-D-Ala-His- 31.6 224 19.6 2500D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(D-Ala-Nle))-c(Cys-D-Ala- 16.0 63.9 8.64 1820His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Val-Nle))-c(Cys-D-Ala-His- 33.7 132 40.2 3210D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Leu-Nle))-c(Cys-D-Ala-His- 48.3 534 74.1 3290D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala-His- 40.8 870 137 3560D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Aib-Nle))-c(Cys-D-Ala-His- 17.7 73.6 8.40 2120D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His- 7.92 46.4 6.70 21.3D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His- 20.9 69.7 8.32 50.0D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His- 12.9 38.5 3.53 27.1D-Phe-Arg-Trp-Pen)-NH₂ (SEQ ID NO: 280)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His- 127 811 10.4 381D-Phe-Arg-Trp-Pen)-NH₂ (SEQ ID NO: 280)Hydantoin(C(O)-(Ala-Gly))-c(Cys-D-Ala-His- 13.9 38.4 5.73 18.9D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala- 11.7 73.1 4.28 34.7His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Aib-Gly))-c(Cys-D-Ala-His- 36.8 290 13.7 133D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Val-Gly))-c(Cys-D-Ala-His- 15.3 160 8.66 33.4D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Ile-Gly))-c(Cys-D-Ala-His- 11.6 194 11.5 28.9D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Leu-Gly))-c(Cys-D-Ala-His- 19.3 331 26.7 44.6D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-Glu-His- 9.49 124 2.95 2260D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-Glu-His- 4.30 78.0 1.77 4540D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 287)Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D- 8.59 94.1 2.44 7760Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D- 5.68 55.5 2.44 4220Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 285)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His- 2.65 41.3 4.17 650D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala- 3.52 48.7 5.78 872His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala- 3.51 29.2 6.04 914His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO288)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His- 1.14 01.7 4.53 783D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 286)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His- 11.9 7.43 0.195 14.6D-2-Nal-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 282) TABLE 7C - Binding Constantsfor Formula (VII) Examples Ki Ki Ki Ki Formula (VII) Compounds hMC1 hMC3hMC4 hMC5 c[Hydantoin(C(O)-(Aib-Cys))-D-Ala-His-D- 47.6 1100 47.1 >10000Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Val-Cys))-D-Ala-His-D- 21.2 730 34.5 >10000Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Leu-Cys))-D-Ala-His-D- 47.4 1550 27.9 >10000Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Ile-Cys))-D-Ala-His-D-Phe- 53.4 1760 41.6 >10000Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(A6c-Cys))-D-Ala-His-D- 38.5 1760 53.2 9270Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D-Phe- 15.6 305 8.92 3070Arg-Trp-Cys]-NH₂ (SEQ ID NO: 291)

TABLE 8 Radioligand Binding Assay Data for Selected Compounds Ki Ki KiKi Compound hMC1-R hMC3-R hMC4-R hMC5-RAc-Tyr-Arg-c(Cys-D-Ala-His-D-Phe- 8.53 21.2 3.72 714 Arg-Trp-Cys)-NH₂(SEQ ID NO: 292) Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe- 6.09 34.9 2.02 864Arg-Trp-Cys)-NH₂ (SEQ ID NO: 292) Ac-1-Nal-Arg-c(Cys-D-Ala-His-D-Phe-6.27 36.4 1.53 888 Arg-Trp-Cys)-NH₂ (SEQ ID NO: 292)Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe- 1.48 14.8 2.34 491 Arg-Trp-Cys)-NH₂(SEQ ID NO: 292) Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe- 4.7 42 2.25 1470Arg-Trp-Cys)-NH₂ (SEQ ID NO: 292) Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-0.323 1.33 1.95 786 Arg-Trp-Cys)-NH₂ (SEQ ID NO: 292)

Melanocortin Functional Activity and Selectivity

The compounds of the present invention will interact preferentially(i.e., selectively) to MC-4 relative to the other melanocortinreceptors. Selectivity is particularly important when the compounds areadministered to humans or other animals to minimize the number of sideeffects associated with their administration. MC-4 selectivity of acompound is defined herein as the ratio of the EC₅₀ of the compound foran MC-1 receptor (EC₅₀-MC-1) over the EC₅₀ of the compound for the MC-3(EC₅₀-MC-3)/MC-4 (EC₅₀-MC-4) receptor, the EC₅₀ values being measured asdescribed above. The formulas are as follows:

MC-3 selectivity=[EC ₅₀ −MC-1]/[EC ₅₀ −MC-3]

MC-4 selectivity=[EC ₅₀ −MC-1]/[EC ₅₀ −MC-4]

A compound is defined herein as being “selective for the MC-3 receptor”when the above mentioned ratio “MC-3-selectivity” is at least about 10,preferably at least about 100, and more preferably at least about 500.

A compound is defined herein as being “selective for the MC-4 receptor”when the above mentioned ratio “MC-4-selectivity” is at least about 10,preferably at least about 100, and more preferably at least about 500.

One skilled in the art would know that procedures similar to thosedescribed herein may be used to assay the binding activities of thecompounds of the invention to melanocortin receptor molecules.

Cyclic AMP Bioassay

Intracellular cyclic AMP (cAMP) levels were determined by anelectrochemiluminescence (ECL) assay (Meso Scale Discovery®,Gaithersburg, Md.; referred to hereinafter as MSD). CHO-K1 cells stablyexpressing the hMC receptor subtypes were suspended in RMPI 1640® assaybuffer (RMPI 1640 buffer contains 0.5 mM isobutylmethylxanthine (IBMX),and 0.2% protein cocktail (MSD blocker A)). Transgenic CHO-K1 cellsstably expressing hMC receptor subtypes 1, 3, 4 or 5 were dispensed at adensity of approximately 7,000 cells/well in 384-well Multi-Array®plates (MSD) containing integrated carbon electrodes and coated withanti-cAMP antibody. Increasing concentrations of the test compounds wereadded and the cells were incubated for approximately 40 minutes atapproximately 37° C. Following this incubation, lysis buffer(HEPES-buffered saline solution with MgCl₂ and Triton X-100® at ph 7.3)containing 0.2% protein cocktail and 2.5 nM TAG™ ruthenium-labeled cAMP(MSD) was added and the cells were incubated for approximately 90minutes at room temperature. At the end of the second incubation periodread buffer (Tris-buffered solution containing an ECL co-reactant andTriton X-100 at ph 7.8) was added and the cAMP levels in the celllysates were immediately determined by ECL detection with a SectorImager 6000 reader® (MSD). Data were analyzed using a computer-assistednon-linear regression analysis (XL fit; IDBS) and reported as either anEC₅₀ value or a Kb value.

EC₅₀ represents the concentration of an agonist compound needed toobtain 50% of the maximum reaction response, e.g., 50% of the maximumlevel of cAMP as determined using the assay described above. The Kbvalue reflects the potency of an antagonist and is determined by Schildanalysis. In brief, concentration-response curves of an agonist arecarried out in the presence of increasing concentrations of anantagonist. The Kb value is the concentration of antagonist which wouldproduce a 2-fold shift in the concentration-response curve for anagonist. It is calculated by extrapolating the line on a Schild plot tozero on the y-axis.

A selection of compounds was tested using the above-discussed assays andthe results are reported in Tables 9, 10, 11, and 12.

TABLE 9 cAMP Bioassay Data for Selected Compounds Table 9A EC₅₀ EC₅₀EC₅₀ EC₅₀ EC₅₀ hMC1-R/ SEQ ID Compound hMC1-R hMC3-R hMC4-R hMC5-R MC4-RNO: Ac-Arg-c(Cys-D- 5.79 5.25 0.313 1630 18.0 SEQ ID Ala-His-D-Phe- NO:50 Arg-Trp-Cys)-NH₂ Ac-D-Arg-c(Cys-D- 6.17 5.6 0.397 1020 16.0 SEQ IDAla-His-D-Phe- NO: 50 Arg-Trp-Cys)-NH₂ Ac-D-Arg-c(Cys-D- 26.5 10.5 0.4932440 54.0 SEQ ID Ala-His-D-Phe- NO: 51 Arg-Trp-Pen)-NH₂ Ac-D-Arg-c(Cys-8.43 32.4 0.959 2140 9.0 SEQ ID His-D-Phe-Arg- NO: 52 Trp-Gaba-Pen)-NH₂Ac-Arg-c(Cys-His- 4.23 8.09 0.719 23.2 6.0 SEQ ID D-Phe-Arg-Trp- NO: 52Gaba-Pen)-NH₂ Ac-Arg-c(Cys-D- 48.3 13.3 0.79 10000 61.0 SEQ IDAla-His-D-Phe- NO: 51 Arg-Trp-Pen)-NH₂ Ac-D-Arg-c(Asp- 1.48 5.76 0.078297 19.0 SEQ ID His-D-Phe-Arg- NO: 53 Trp-Ala-Lys)-NH₂ Ac-Arg-c(Asp-His-1.39 2.89 0.055 467 25.0 SEQ ID D-Phe-Arg-Trp- NO: 53 Ala-Lys)-NH₂ Table9B EC₅₀ EC₅₀ EC₅₀ EC₅₀ EC₅₀ hMC1-R/ SEQ ID Compound hMC1-R hMC3-R hMC4-RhMC5-R MC4-R NO: Ac-Nle-c(Cys-D-Ala-His- 2.4 0.33 0.078 420 31 SEQ IDD-Phe-Arg-Trp-Cys)- NO: 7 NH₂ D-Phe-c(Cys-His-D- 0.35 1.1 0.11 0.37 3SEQ ID (Et)Tyr-Arg-Trp-β-Ala- NO: 24 D-Cys)-Thr-NH₂ Nle-c(Cys-His-D-Phe-0.31 0.27 0.018 3.1 17 SEQ ID Arg-Trp-Apn-Cys)-NH₂ NO: 27Ac-Nle-c(Cys-His-D-Phe- 0.28 0.24 0.028 3.9 10 SEQ IDArg-Trp-Gaba-Pen)-NH₂ NO: 32 Nle-c(Cys-His-D-Phe- 0.37 0.1 0.021 1.7 18SEQ ID Arg-Trp-Gaba-Cys)-NH₂ NO: 34 Ac-Nle-c(Asp-His-D- 0.834 0.1450.128 2.79 6.52 SEQ ID Phe-Arg-Trp-β-Ala-Lys)- NO: 1 NH₂Ac-Nle-c(Cys-His-D-Phe- 0.76 0.199 0.0492 1.73 15.45 SEQ IDArg-Trp-Apn-Cys)-NH₂ NO: 2 Ac-Cha-c(Asp-His-D- 3.26 0.189 0.0949 30.234.35 SEQ ID Phe-Arg-Trp-Gaba-Lys)- NO: 6 NH₂ Ac-Nle-c(Asp-His-D- 1.370.628 0.131 3.48 10.46 SEQ ID Phe-Arg-Trp-Gaba-Lys)- NO: 6 NH₂Ac-hCha-c(Asp-His-D- 2.27 3.32 7.24 415 0.31 SEQ IDPhe-Arg-Trp-Gaba-Lys)- NO: 11 NH₂ Ac-Nle-c(Pen-D-Ala-His- ND 1.89 0.531ND ND SEQ ID D-Phe-Arg-Trp-Cys)- NO: 21 NH₂ Ac-Nle-c(Cys-D-Ala-His- 14.32.03 0.183 2240 78.14 SEQ ID D-Phe-Arg-Trp-Pen)- NO: 22 NH₂D-Phe-c(Cys-His-D- 0.345 2.71 5376 2.38 0.06 SEQ ID(Et)Tyr-hArg-Trp-β-Ala- NO: 24 D-Cys)-Thr-NH₂ D-Phe-c(Cys-His-D- 0.68581.8 86.9 31.8 0.01 SEQ ID (Et)Tyr-hArg-Bip-β-Ala- NO: 26 D-Cys)-Thr-NH₂Ac-Nle-c(Asp-D-Ala-His- 0.931 3.22 1.65 >10000 0.56 SEQ IDD-Phe-Arg-Bal-Lys)-NH₂ NO: 28 Ac-Nle-c(Cys-D-Leu-His- 3.24 0.465 0.091578.5 35.41 SEQ ID D-Phe-Arg-Trp-Cys)- NO: 30 NH₂ Ac-Nle-c(Cys-D-Cha-0.819 0.541 0.453 45.3 1.81 SEQ ID His-D-Phe-Arg-Trp-Cys)- NO: 30 NH₂Table 9C EC50 Kb Kb EC50 SEQ ID Compound hMC1-R hMC3-R MC4-R hMC5-R NO:Ac-Nle-c(Cys-D-Ala-His-D-2- 17.6 12.4 38.8 11.8 SEQ IDNal-Arg-Trp-Cys)-NH₂ NO: 16 Ac-Nle-c(Asp-His-D-2-Nal-Arg- 0.619 2.980.109 0.189 SEQ ID Trp-Ala-Lys)-NH₂ NO: 38 Ac-Nle-c(Asp-His-D-2-Nal-Arg-0.913 0.536 0.346 0.489 SEQ ID Trp-β-Ala-Lys)-NH₂ NO: 38Ac-Nle-c(Cys-His-D-2-Nal-Arg- 0.231 18.4 0.782 0.153 SEQ IDTrp-Gaba-Cys)-NH₂ NO: 39 Ac-Nle-c(Cys-His-D-2-Nal-Arg- 0.581 10.8 0.9670.126 SEQ ID Trp-Ahx-Cys)-NH₂ NO: 39 Ac-hPhe-c(Asp-His-D-2-Nal-Arg-0.413 9.32 0.824 0.307 SEQ ID Trp-Gaba-Lys)-NH₂ NO: 40Ac-Cha-c(Asp-His-D-2-Nal-Arg- 1.27 3.02 0.442 0.736 SEQ IDTrp-Gaba-Lys)-NH₂ NO: 40 Ac-Nle-c(Cys-D-Ala-His-D-2- 383 61.5 53.6 2842SEQ ID Nal-Arg-1-Nal-Cys)-NH₂ NO: 16 Table 9D EC₅₀ Kb Kb EC₅₀ SEQ IDCompound hMC1-R hMC3-R MC4-R hMC5-R NO: Ac-Arg-c(Cys-D-Ala-His-D-2- 1935.72 1.58 1111 SEQ ID Nal-Arg-Trp-Cys)-NH₂ NO: 49 ND = not determined

Table 10A EC₅₀ Kb Kb EC₅₀ Compound hMC1-R hMC3-R hMC4-R hMC5-RAc-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 66.1 33.4 0.687 6.840Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269)Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg- ND 4500 105 NDArg-Arg-Nle-c(Asp-His-D-2-Nal-Arg-Trp- Lys)-NH₂ (SEQ ID NO: 60)Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg- ND 395 16.8 NDArg-Arg-Doc-Nle-c(Asp-His-D-2-Nal-Arg- Trp-Lys)-NH₂ (SEQ ID NO: 61)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β- ND 207 18.5 NDAla-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO: 62)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β- ND 220 4.07 NDAla-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO: 62)H-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- ND 261 3.11 NDDoc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 63)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- ND 14.1 22.8 NDPro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys-Lys- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ IDNO: 64) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly- ND 233 26.0 NDCys)-Pro-Pro-Lys-Asp-Tyr-Gly-Arg-Lys- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 65) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β- 1.39 16.2 7.940.839 Ala-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ IDNO: 66) Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- 3.65 19.4 3.73 1.61Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 67) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly- ND 17.7 1.49 NDCys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 68)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 6.3 70.0 1.66 38.2Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg- Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 69) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 12.1 30.3 1.8170.0 Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 69)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 33.6 140 12.2 66.9Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 269 105 5.92 104Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269) Ac-cCys-Glu-His-D-2-Nal-Arg-Bal-Ala- 690 70.7 4.56 177Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 269)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- 3.23 8.97 4.61 2.86Doc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 70)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 52.0 170 6.14 328Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 72) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 146 104 32.0 1400Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg- Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 73) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 114 44.6 28.4 879Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 74)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 67.1 439 46.5 582Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Aib-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 79)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 144 116 8.93 819Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 80) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 36.0 46.5 11.4 56.1Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 80) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 93.0 71 15.9 >10000Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 81) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 39.7 30.9 6.66501 Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 82) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 35.2 22.9 12.6199 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 82) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 29.1 13.6 13.4204 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 86.1 41.7 19.4 2360Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 83) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 38.3 20.221.2 >10000 Cys)-Pro-Pro-Arg-Asp-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 84)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 68.6 153 33.2 >10000Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Arg- Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 83) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 70.4 28618.6 >10000 Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 33.1 65.1 15.3 1720Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 89) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 88.2 10.6 17.4 514Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 88) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 58.7 39.3 10.3 460Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 90)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 45.4 12.7 12.7 162Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 91) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 309 22.8 17.1570 Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 92)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 7.86 10.5 0.843 4900Cys)-β-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO:139) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 29.7 25.6 7.37 82.9Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 15.2 14.6 4.52 36.8Cys)-Pro-Pro-Lys-Asp-βAla-Tyr-Gly-Arg-Lys-Lys-Arg-Gln-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 75)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 6.7 9.38 11.7 46.2Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Gln-Arg-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 76)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 7.9 41.7 10.9 62.4Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-Arg-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 77)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 16.9 36.0 7.12 58.9Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Arg-Gln-Arg-NH₂ (SEQ ID NO: 78)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 16.4 20.8 7.31 44.2Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Arg-Gln-Arg-Arg-NH₂ (SEQ ID NO: 85)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 12.0 13.7 9.38 54.2Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-Lys-Lys-Arg-Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO: 86)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala- 7.5 12.2 7.61 51.7Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg- Lys-Lys-Arg-Arg-Arg-Arg-Arg-Gln-NH₂ (SEQ ID NO: 87) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 43.3 2155.87 1286 Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 37.9 112 41.1 1798Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 71) Table 10B EC50 EC50EC50 EC50 Compound hMC1-R hMC3-R hMC4-R hMC5-RAc-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 4.70 4.56 0.634 147Cys)-(Doc)2-Tyr-Gly-Arg-Lys-Lys-Arg- Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO:136) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 5.90 7.73 1.02 2890Cys)-β-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Gln- Arg-Arg-Arg-Arg-NH₂ (SEQ ID NO:137) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 0.481 7.32 0.964 2010Cys)-β-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 7.15 9.37 1.25 1570Cys)-β-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg- Arg-Arg-NH₂ (SEQ ID NO: 138)Table 10C EC₅₀ Kb Kb EC₅₀ Compound hMC1-R hMC3-R hMC4-R hMC5-RAc-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β- ND ND ND NDAla-Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib- 770 221 4.52 869Cys)-Pro-Pro-Lys-Asp-NH₂ (SEQ ID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 29 22.6 16.7 173Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 95)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 102 26.3 14.6 261Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 96)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 26.6 101 9.34 351Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 97) Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala- 45.5 181 6.35149 Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 23.7 9.22 5.87 39.7Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 99) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala- 34.7 15.0 8.68 28.2Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 19.1 106 4.59 100Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Lys-Arg- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 105) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 19.8 37.8 8.43 158Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg- Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 100) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 11.2 52.19.45 95.7 Cys)-Pro-Pro-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 33.8 93.6 4.42 89.5Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Arg- Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 102) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 232 68.8 10.0 250Cys)-Pro-Pro-Lys-Asp-β-Ala-Arg-Arg-Lys- Arg-Arg-Gln-Arg-Arg-Arg-NH₂ (SEQID NO: 104) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala- 32.2 98.3 5.23 194Cys)-Pro-Pro-Lys-Asp-β-Ala-Gly-Arg-Lys- Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH₂(SEQ ID NO: 103) Table 10D EC50 EC50 EC50 EC50 Compound hMC1-R hMC3-RhMC4-R hMC5-R Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 5.66 4.70 0.422 1551Cys)-β-Ala-Tyr-Gly-Arg-Arg-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO:141) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 7.57 4.18 0.600 1792Cys)-β-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO:142) Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 2.36 2.74 0.260 500Cys)-β-Ala-Gly-Arg-Arg-Lys-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 2.81 3.29 0.298 566Cys)-β-Ala-Gly-Arg-Lys-Arg-Arg-Arg- Gln-Arg-Arg-Arg-NH₂ (SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 1.86 1.39 0.367 165Cys)-β-Ala-Arg-Arg-Lys-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO: 143)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- 2.06 1.61 0.394 199Cys)-β-Ala-Arg-Lys-Arg-Arg-Arg-Gln- Arg-Arg-Arg-NH₂ (SEQ ID NO: 144) ND= not determined

TABLE 11 Intracellular Cyclic AMP (cAMP) Levels for Formula (I) ExamplesTable 11A EC₅₀ EC₅₀ EC₅₀ EC₅₀ Formula (V) Compounds hMC1 hMC3 hMC4 hMC5c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe- — 218 5.42 — Arg-Trp-Cys]-NH₂(SEQ ID NO: 271) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- — 22.3 3.62 —Arg-Trp-Lys]-NH₂ (SEQ ID NO: 276)c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- — 39.2 4.94 — Arg-Trp-Orn]-NH₂(SEQ ID NO: 276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- 56.7 18.20.182 >10000 Arg-Trp-Dap]-NH₂ (SEQ ID NO: 276)c[Hydantoin(C(O)-(Asp-D-Ala))-His-D- 56.6 88.6 4.50 9300Phe-Arg-Trp-Orn]-NH₂ (SEQ ID NO: 273)c[Hydantoin(C(O)-(Asp-D-Ala))-His-D- — 49.3 2.12 — Phe-Arg-Trp-Dap]-NH₂(SEQ ID NO: 273) TABLE 11B - EC₅₀ EC₅₀ EC₅₀ EC₅₀ Formula (VI) CompoundshMC1 hMC3 hMC4 hMC5 Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His- 54.3 12.20.177 >10000 D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His- 124 8.05 0.214 >10000D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(A6c-Nle))-c(Cys-D-Ala- — 4.89 1.80 —His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(D-Ala-Nle))-c(Cys-D-Ala- — 2.56 1.47 —His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Val-Nle))-c(Cys-D-Ala- — 4.61 0.977 —His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Leu-Nle))-c(Cys-D-Ala- — 9.68 1.83 —His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala- — 9.97 13.9 —His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 284)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala- 14.2 2.46 0.336 201His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala- 17.0 21.5 0.584 352His-D-Phe-Arg-Trp-Pen)-NH₂ (SEQ ID NO: 280)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala- 40.2 8.90 0.495 8300His-D-Phe-Arg-Trp-Pen)-NH₂ (SEQ ID NO: 280)Hydantoin(C(O)-(Ala-Gly))-c(Cys-D-Ala- 17.6 2.23 0.241 516His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala- 4.70 2.22 0.309 355His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-Glu- 18.0 17.1 0.160 2710His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-Glu- 12.9 10.3 0.125 7440His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 287)Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His- 8.83 7.86 0.0979 4010D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 278)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His- 9.97 3.63 0.0687 335D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 285)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala- 8.81 18.2 0.503 3560His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D- 11.5 23.2 0.513 3950Ala-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 279)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D- 7.53 11.6 0.435 9840Ala-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 288)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala- 8.85 5.17 0.599 3610His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 286)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala- 96.6 13.1 21.2 103His-D-2-Nal-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 282) TABLE 11C EC₅₀ EC₅₀ EC₅₀EC₅₀ Formula (VII) Compounds hMC1 hMC3 hMC4 hMC5c[Hydantoin(C(O)-(Aib-Cys))-D-Ala-His-D- — 6.28 0.407 —Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Val-Cys))-D-Ala-His-D- — 3.77 0.214 —Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Leu-Cys))-D-Ala-His-D- — 4.72 0.428 —Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Ile-Cys))-D-Ala-His-D- — 8.51 1.85 —Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(A6c-Cys))-D-Ala-His-D- — 5.66 1.72 —Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 290)c[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D- 14.5 21.8 0.576 1780Phe-Arg-Trp-Cys]-NH₂ (SEQ ID NO: 291)

TABLE 12 cAMP Bioassay Data for Selected Compounds EC₅₀ EC₅₀ EC₅₀ EC₅₀Compound hMC1-R hMC3-R hMC4-R hMC5-R Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-6.42 2.39 0.194 1540 Arg-Trp-Cys)-NH₂ (SEQ ID NO: 292)Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe- 9.66 6.11 0.275 1730Arg-Trp-Cys)-NH₂ (SEQ ID NO: 292) Ac-1-Nal-Arg-c(Cys-D-Ala-His-D- 8.674.21 0.363 1320 Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO: 292)Ac-Trp-Arg-c(Cys-D-Ala-His-D- 5.78 3.95 0.219 2580 Phe-Arg-Trp-Cys)-NH₂(SEQ ID NO: 292)

In Vivo Studies

Compounds of the present invention can be and were tested for an effectupon insulin resistance and/or body weight according to the followingprocedures. One skilled in the art would know that procedures similar tothose described herein may be used to assay the effect of the compoundsof the invention upon insulin resistance and/or body weight.

Ligand compounds activating melanocortin receptors tested in the in vivostudies were as follows (Table 13):

TABLE 13 Ligand Code Structure Compound AAc-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp- Cys)-NH₂ SEQ ID NO: 50 Compound BHydantoin(C(O)-(Arg-Gly))-c(Cys- Glu-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ IDNO: 278)

Acute Feeding Experiments (Fasting)

Male Sprague Dawley rats (250 g) were housed in individual cages andmaintained under 12:12 hour light:dark conditions. The rats were fastedfor 18 hours prior to the start of the experiment with water availablead libitum. At time 0, the rats were injected subcutaneously (sc) withselected compounds at doses of 100 nmole/kg, or with vehicle, and wereprovided with food. Individual food consumption was measured at about 2,4 and 6 hours after injection. Data for selected compounds of theinvention are reported in FIG. 1.

Chronic Feeding Experiments

Male, Sprague Dawley rats that had been fed either a normal diet (300 g;Research Diets 12450) or a high fat diet (400 g; Research Diets 12451)for 10 weeks prior to the start of the experiment were housed inindividual cages and maintained under 12:12 hour light:dark conditionswith both food and water available ad libitum. The rats wereanesthetized and implanted subcutaneously with an osmotic mini pump(Alzet, Cupertino, Calif.). The pumps delivered either Compound A orCompound B at doses of 75, 300 or 1200 nmole/kg/day, or vehicle for 7days. Individual body weight and food consumption were measured daily.

On day 7 rats were anesthetized and fit with a jugular-right atrialcannula. On day 8 an iv glucose tolerance test was performed and bloodsamples were withdrawn into heparinized syringes at time −10 and 0.Immediately after the time 0 blood sample, the rats were injected withglucose (1 g/kg) via the indwelling cannula. Subsequent blood sampleswere withdrawn at 2.5, 5, 10, 20 and 40 minutes later. Plasma levels ofglucose (Diagnostic Chemicals Limited) and insulin (Alpco) weredetermined by commercially available kits. Results are shown in FIGS.2A-D and 3A-D.

Glucose Tolerance Tests

Male, C₅₇BL/6 mice that had been fed either a normal diet (30 g;Research Diets 12450) or a high fat diet (45 g; Research Diets 12452)for 12 weeks prior to the start of the experiment were housed inindividual cages and maintained under 12:12 hour light:dark conditionswith both food and water available ad libitum. The mice wereanesthetized and implanted subcutaneously with an osmotic mini pump(Alzet, Cupertino, Calif.). The pumps delivered Compound A at doses of200, 600 or 1800 nmole/kg/day, or vehicle for 14 days. On day 14 themice were fasted for 18 hours or overnight. On day 15 an glucosetolerance test was performed by injecting the mice with glucose (2 g/kg)ip. Blood samples were taken by tail stick at 0, 15, 30, 60 and 180minutes after the glucose injection and blood glucose level was measuredusing an Accu-Chek glucometer. Results are shown in FIG. 4.

Male, Lep^(ob)/Lep^(ob) mice (50 g) were group housed maintained under12:12 hour light:dark conditions with both food and water available adlibitum. The mice were fasted for 18 hours or overnight and an ipglucose tolerance test was performed. Mice were injected with Compound Aip at a dose of 6.4 μmole/kg at −15 minutes and a blood sample was takenby tail stick. At time 0 mice were injected ip with glucose (1 g/kg) andblood samples were taken by tail stick at 0, 15, 30, 60 and 90 minuteslater and blood glucose level was measured using Glucometer Elite XL(Bayer Corporation). Results are shown in FIG. 5.

Administration and Use

The peptides of this invention can be provided in the form ofpharmaceutically acceptable salts. Examples of such salts include, butare not limited to, those formed with organic acids (e.g., acetic,lactic, maleic, citric, malic, ascorbic, succinic, benzoic,methanesulfonic, toluenesulfonic, or pamoic acid), inorganic acids(e.g., hydrochloric acid, sulfuric acid, or phosphoric acid), andpolymeric acids (e.g., tannic acid, carboxymethyl cellulose, polylactic,polyglycolic, or copolymers of polylactic-glycolic acids). A typicalmethod of making a salt of a peptide of the present invention is wellknown in the art and can be accomplished by standard methods of saltexchange. Accordingly, the TFA salt of a peptide of the presentinvention (the TFA salt results from the purification of the peptide byusing preparative HPLC, eluting with TFA containing buffer solutions)can be converted into another salt, such as an acetate salt, bydissolving the peptide in a small amount of 0.25 N acetic acid aqueoussolution. The resulting solution is applied to a semi-prep HPLC column(Zorbax®, 300 SB, C-8). The column is eluted with: (1) 0.1N ammoniumacetate aqueous solution for 0.5 hours; (2) 0.25N acetic acid aqueoussolution for 0.5 hours; and (3) a linear gradient (20% to 100% ofsolution B over 30 minutes) at a flow rate of 4 ml/min (solution A is0.25N acetic acid aqueous solution; solution B is 0.25N acetic acid inacetonitrile/water, 80:20). The fractions containing the peptide arecollected and lyophilized to dryness.

As is well known to those skilled in the art, the known and potentialuses of peptides with melanocortin receptor (MC-R) agonist or antagonistactivity is varied and multitudinous, thus the administration of thecompounds of this invention for purposes of eliciting an agonist effectcan have the same effects and uses as melanocortin itself.

Accordingly, the present invention includes within its scopepharmaceutical compositions comprising, as an active ingredient, atleast one of the compounds of formula (I) in association with apharmaceutically acceptable carrier.

The dosage of active ingredient in the compositions of this inventionmay be varied; however, it is necessary that the amount of the activeingredient be such that a suitable dosage form is obtained. The selecteddosage depends upon the desired therapeutic effect, on the route ofadministration, and on the duration of the treatment. In general, aneffective dosage for the activities of this invention is in the range of1×10⁻⁷ to 200 mg/kg/day, preferably 1×10⁴ to 100 mg/kg/day which can beadministered as a single dose or divided into multiple doses.

The compounds of this invention can be administered by oral, parenteral(e.g., intramuscular, intraperitoneal, intravenous or subcutaneousinjection, or implant), nasal, vaginal, rectal, sublingual or topicalroutes of administration and can be formulated with pharmaceuticallyacceptable carriers to provide dosage forms appropriate for each routeof administration.

Solid dosage forms for oral administration include capsules, tablets,pills, powders and granules. In such solid dosage forms, the activecompound is admixed with at least one inert pharmaceutically acceptablecarrier such as sucrose, lactose, or starch. Such dosage forms can alsocomprise, as is normal practice, additional substances other than suchinert diluents, e.g., lubricating agents such as magnesium stearate. Inthe case of capsules, tablets and pills, the dosage forms may alsocomprise buffering agents. Tablets and pills can additionally beprepared with enteric coatings.

Liquid dosage forms for oral administration include pharmaceuticallyacceptable emulsions, solutions, suspensions, syrups, the elixirscontaining inert diluents commonly used in the art, such as water.Besides such inert diluents, compositions can also include adjuvants,such as wetting agents, emulsifying and suspending agents, andsweetening, flavoring and perfuming agents.

Preparations according to this invention for parenteral administrationinclude sterile aqueous or non-aqueous solutions, suspensions, oremulsions. Examples of non-aqueous solvents or vehicles are propyleneglycol, polyethylene glycol, vegetable oils, such as olive oil and cornoil, gelatin, and injectable organic esters such as ethyl oleate. Suchdosage forms may also contain adjuvants such as preserving, wetting,emulsifying, and dispersing agents. Preparations may be sterilized by,for example, filtration through a bacteria-retaining filter, byincorporating sterilizing agents into the compositions, by irradiatingthe compositions, or by heating the compositions. Preparations can alsobe manufactured in the form of sterile solid compositions which can bedissolved in sterile water or some other sterile injectable mediumimmediately before use.

Compositions for rectal or vaginal administration are preferablysuppositories which may contain, in addition to the active substance,excipients such as cocoa butter or a suppository wax.

Compositions for nasal or sublingual administration are also preparedwith standard excipients well known in the art.

Further, a compound of this invention can be administered in a sustainedrelease composition such as those described in the following patents andpatent applications. U.S. Pat. No. 5,672,659 teaches sustained releasecompositions comprising a bioactive agent and a polyester. U.S. Pat. No.5,595,760 teaches sustained release compositions comprising a bioactiveagent in a gelable form. U.S. Pat. No. 5,821,221 teaches polymericsustained release compositions comprising a bioactive agent andchitosan. U.S. Pat. No. 5,916,883 teaches sustained release compositionscomprising a bioactive agent and cyclodextrin. The teachings of theforegoing patents and applications are incorporated herein by reference.

1. A method of treating insulin resistance in a subject in need thereof,comprising peripheral administration of an effective amount of amelanocortin receptor δ agonist to treat said insulin resistance in saidsubject in need thereof.
 2. The method according to claim 1, where insaid melanocortin receptor δ agonist useful to treat insulin resistanceis selected from the group consisting of: SEQ ID NO: 1Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 1Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH₂; SEQ ID NO: 2Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 4Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH₂; SEQ ID NO: 5Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 6Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 7Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 8Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 9Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 10Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH₂; SEQ ID NO: 11Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 12n-butanoyl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 11Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 13Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 13Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH₂; SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH₂; SEQ ID NO: 17n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 17n-butanoyl-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH₂; SEQ ID NO: 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH₂; SEQ ID NO: 59Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 19Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH₂; SEQ ID NO: 20Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH₂; SEQ ID NO: 21Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 22Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 22Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 23D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 25D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 24D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 26D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH₂; SEQ ID NO: 27Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH₂; SEQ ID NO: 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH₂; SEQ ID NO: 29Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEQ ID NO: 30Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 30Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 31Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 32Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 32Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 33Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 33Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 34Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 34Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 35Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 36Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 37Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH₂; SEQ ID NO: 40Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 40Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH₂; SEQ ID NO: 41Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH; SEQ ID NO: 42Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH; SEQ ID NO: 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; SEQ ID NO: 42Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; SEQ ID NO: 41Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; SEQ ID NO: 44Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 44Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH; SEQ ID NO: 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH; SEQ ID NO: 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH; SEQ ID NO: 47Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEQ ID NO: 48Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; SEQ ID NO: 49Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; SEQ ID NO: 50Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 50Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; SEQ ID NO: 51Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 52Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 52Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH₂; SEQ ID NO: 51Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; SEQ ID NO: 53Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 53Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH₂; SEQ ID NO: 35Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH₂; SEQ ID NO: 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH₂; SEQ ID NO: 55Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 55Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH₂; SEQ ID NO: 56Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 56Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH₂; SEQ ID NO: 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH₂; SEQ ID NO: 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH₂; SEQ ID NO: 58Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH₂; (SEQ ID NO: 60)Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH₂;(SEQ ID NO: 61)Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH₂;(SEQ ID NO: 62)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂;(SEQ ID NO: 62)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂;(SEQ ID NO: 63)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂;(SEQ ID NO: 64)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)₂-Lys-Asp-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 65)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 66)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂;(SEQ ID NO: 67)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 68)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 69)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 69)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 70)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂;(SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 72)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 73)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 74)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 75)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂; (SEQ ID NO: 76)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-Gln-(Arg)₅-NH₂; (SEQ ID NO: 77)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)₅-NH₂; (SEQ ID NO: 78)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₄-Gln-Arg-NH₂; (SEQ ID NO: 79)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 80)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 80)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂;(SEQ ID NO: 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 81)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂;(SEQ ID NO: 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂;(SEQ ID NO: 84)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂;(SEQ ID NO: 85)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₃-Gln-(Arg)₂-NH₂; (SEQ ID NO: 86)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)₂-(Arg)₅-NH₂; (SEQ ID NO: 87)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₅-Gln-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 89)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 90)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 91)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 95)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 96)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 97)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 98)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 99)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 104)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 105)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 100)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 102)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 103)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂; (SEQ ID NO: 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 118)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 118)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 119)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂;(SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 124)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₆-Gln-(Arg)₃-NH₂;(SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 126)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 126)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 128)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 128)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 130)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 130)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 133)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 134)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 134)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 135)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 135)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Arg-Asp-β-Ala-Tyr-Gly-(Arg)₆-Gln-(Arg)₃-NH₂; (SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 137)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)₂-Arg-Gln-(Arg)₄-NH₂;(SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)₂-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 139)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 140)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂; (SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂;(SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂;(SEQ ID NO: 142)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂;(SEQ ID NO: 143)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₂-Lys-(Arg)₂-Gln-(Arg)₃-NH₂;(SEQ ID NO: 144)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)₃-Gln-(Arg)₃-NH₂;(SEQ ID NO: 148)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 148)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 149)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH_(2;;)(SEQ ID NO: 149)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 151)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 151)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 152)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 152)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 154)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 153)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 154)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 155)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 155)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 157)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 156)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 156)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 157)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 158)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 158)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 159)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 160)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 161)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 162)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 164)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 163)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 163)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 164)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 165)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 165)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 166)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 166)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 168)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 167)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 167)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 168)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 170)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 169)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 169)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 170)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 171)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 171)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 173)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 172)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 172)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 173)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 175)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 176)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 177)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 178)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 179)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 180)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 181)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 182)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 183)Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 184)Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 183)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 185)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 186)Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 185)Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 186)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 187)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 189)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 190)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 189)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 190)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 191)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 191)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 193)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 194)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 193)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 194)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 195)Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 196)Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 197)Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 198)Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 199)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 199)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 201)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 202)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 203)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 203)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 204)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 204)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 207)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 206)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 206)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 207)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 208)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 208)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 209)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 210)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 209)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 211)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 212)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 213)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 213)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 267)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 214)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 216)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 214)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 217)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 215)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 216)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 215)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 217)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 220)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 224)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 225)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 224)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 225)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 226)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ ID NO: 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 229)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 230)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 232)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 231)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ ID NO: 232)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 233)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 234)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 235)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 236)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 235)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 236)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 237)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 238)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 237)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 238)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 239)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 240)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 239)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 240)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 241)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 242)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 241)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 242)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 243)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 243)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 245)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 246)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 245)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 246)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 247)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 247)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 249)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 250)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 249)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 250)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 251)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 251)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 253)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 254)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 253)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 254)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 255)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 255)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 257)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 258)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 257)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 258)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 259)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 260)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 259)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 260)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 261)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 262)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 261)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 262)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)₂-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 263)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 264)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQ IDNO: 263)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₃-NH₂;(SEQ ID NO: 264)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₃-NH₂; (SEQID NO: 265)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 266)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQ IDNO: 265)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-Tyr-Gly-(Arg)₅-Gln-(Arg)₄-NH₂;(SEQ ID NO: 266)Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)₂-(Arg)₅-Gln-(Arg)₄-NH₂; (SEQID NO: 268)Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)₂-Lys-Asp-NH_(2;) (SEQID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 269) Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂;(SEQ ID NO: 269)Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 210) Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂;(SEQ ID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQID NO: 270)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)₂-Lys-Asp-NH₂; (SEQ IDNO: 271) c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQID NO: 271) c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 272)c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH₂; (SEQ ID NO:272) c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH₂; (SEQID NO: 273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH₂;(SEQ ID NO: 273)c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH₂; (SEQ ID NO:273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH₂; (SEQ IDNO: 273) c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH₂; (SEQID NO: 275) c[Hydantoin(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQID NO: 274) c[Hydantoin(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ IDNO: 274) c[Hydantoin(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:274) c[Hydantoin(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:275) c[Hydantoin-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH₂; (SEQ ID NO:276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH₂; (SEQ IDNO: 276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH₂; (SEQID NO: 276) c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH₂;(SEQ ID NO: 277) c[Hydantoin(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH₂;(SEQ ID NO: 278)Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 278) Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 278)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 279)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 280)Hydantoin(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 281)Hydantoin(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 281)Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 278)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 279)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 282)Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 282)Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 283)Hydantoin(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 283) Hydantoin(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 283)Hydantoin(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 284)Hydantoin(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 284)Hydantoin(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 285)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 285)Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 286)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 286)Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂; (SEQID NO: 287)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 288)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 288)Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH₂;(SEQ ID NO: 289)Hydantoin(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂,(SEQ ID NO: 290)c[Hydantoin(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 290) c[Hydantoin(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 290)c[Hydantoin(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH₂; (SEQ IDNO: 291) c[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH₂;(SEQ ID NO: 292) Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQID NO: 292) Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ IDNO: 292) Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH₂; (SEQ ID NO:292) Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 292)Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 292)Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 293)H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂; (SEQ ID NO: 292)Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂;

or a pharmaceutically acceptable salt thereof.
 3. The method accordingto claim 2, wherein said compound isAc-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO:50) or apharmaceutically acceptable salt thereof.
 4. The method according toclaim 2, wherein said compound isHydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ IDNO:278) or a pharmaceutically acceptable salt thereof.
 5. The methodaccording to claim 1, wherein said subject is obese or overweight. 6.(canceled)
 7. The method according to claim 1, wherein said subject isnormal weight or lean.
 8. (canceled)
 9. The method according to claim 5,wherein said subject suffers from type II diabetes.
 10. (canceled) 11.The method according to claim 7, wherein said subject suffers from typeII diabetes.
 11. (canceled)
 13. The method according to claim 1, whereinsaid peripheral administration is oral, subcutaneous, intraperitoneal,intramuscular, intravenous, rectal, transdermal or intranasal.
 14. Themethod according to claim 13, wherein said administration is continuous,hourly, four times daily, three time daily, twice daily, once daily,once every other day, twice weekly, once weekly, once every two weeks,once a month, or once every two months. 15-20. (canceled)
 21. The methodaccording to claim 1, wherein said peripheral administration of aneffective amount of a melanocortin receptor δ agonist to treat saidinsulin resistance in a subject need thereof also reduces the bodyweight of said subject in need thereof.
 22. The method according toclaim 21, wherein said compound isAc-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ ID NO:50) or apharmaceutically acceptable salt thereof.
 23. The method according toclaim 21, wherein said compound isHydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH₂ (SEQ IDNO:278) or a pharmaceutically acceptable salt thereof.
 24. The methodaccording to claim 21, wherein said subject is obese or overweight. 25.(canceled)
 26. The method according to claim 24, wherein said obesesubject suffers from type II diabetes.
 27. (canceled)
 28. The methodaccording to claim 21, wherein said peripheral administration is oral,subcutaneous, intraperitoneal, intramuscular, intravenous, rectal,transdermal or intranasal.
 29. The method according to claim 28, whereinsaid administration is continuous, hourly, four times daily, three timedaily, twice daily, once daily, once every other day, twice weekly, onceweekly, once every two weeks, once a month, or once every two months.30-35. (canceled)